This Application is National Stage of International Application Ser. No. PCT/JP98/01753, filed Apr. 16, 1998.
The present invention relates to a medicine and, more particularly, to a thermogenic agent (thermogenesis accelerator) for use as a prophylactic and/or treating drug for obesity and obesity-associated disease and its active compound, namely an aminoketone derivative or a salt thereof.
As treating drugs for obesity, centrally-acting anorexics such as mazindol have been used-clinically However, central anorexics have gastrointestinal side effects such as nausea and vomiting in addition to central side effects such as addiction and, therefore, are indicated only in limited cases, e.g. advanced obesity.
On the other hand, xcex23 adrenergic receptor agonists have been proposed as peripherally-acting antiobesity drugs [Nature, 309, 163-165, 1984; J. Med. Chem., 35, 3081-3084, 1992, etc.]. However, mutations of the xcex23 adrenergic receptor gene have been reported in a fairly large number of obese persons (New Engl. J. Med., 333, 343-347, 1995; Lancet, 346, 1433-1434, 1995; Biochem. Biophys. Res. Commun., 215, 555-560, 1995) and it is logical to assume that the antiobesity effect of any xcex23 adrenergic receptor agonist is self-limited.
As synthetic drugs, aminoketone derivatives having a variety of biological and pharmacological activities have been proposed (Japanese Patent Unexamined Publication No. 140149/1993, WO 9307140, EP 560235, EP 562832, Japanese Patent Unexamined Publication No. 169569/1990, U.S. Pat. No. 5,106,856, Japanese Patent Unexamined Publication No. 22333/1979, Japanese Patent Unexamined Publication No. 167546/1984, EP-A-0378207, Japanese Patent Unexamined Publication No. 206875/1994, Japanese Patent Unexamined Publication No. 206854/1995, Japanese Patent Unexamined Publication No. 309835/1995, WO 9103243, Khim.-Farm., Zh., 21, 569, (1987), Chem. Abstr., 89, 36594y (1978), Journal of the Pharmaceutical Society of Japan, 97, 540 (1977), EP 163537, Chem. Abstr., 91, 211631y (1979), Helvetica Chimica Acta, 51, 1616 (1968), Japanese Patent Unexamined Publication No. 97952/1977, Japanese Patent Unexamined Publication No. 7185/1984, FR-M3635, Chem. Abstr., 67, 54087k (1967), 68, 105121x (1968), 75, 88548s (1971), 76, 153682t (1972)). However, none of the literature discloses, or even suggests, that such derivatives ever have activity validating their use as prophylactic and/or treating drugs for obesity or obesity-associated disease, as lipolytic agents, or as thermogenic agents.
For example, Japanese Patent Unexamied Publication No. 140149/1993 describes a fused heterocyclic derivative of the following chemical formula or a salt thereof as a cholinesterase inhibitor: 
wherein X represents R1xe2x80x94N less than  (R1 represents hydrogen, a hydrocarbon group which may be substituted, or an acyl group which may be substituted), oxygen, or sulfur; R2 reprehsents hydrogen or a hydrocarbon group which may be substituted; ring A represents a benzene ring which may be substituted; k represents an integer of 0-3; m represents an integer of 1-8; and n represents an integer of 1-6. Spedifically described is a compounds of the following formula: 
WO 9307140 discloses a compound of the following formula as a cholinesterase inhibitor: 
wherein ring A represents benzo, thieno, pyrido, pyrazino, pyrimido, furano, seleno, pyrrolo, thiazolo, or imidazolo; R1 represents phenyl, phenyl(C1-6)alkyl, cinnamyl, or heteroarylmethyl (heteroaryl=imidazolo, thiazolo, thieno, pyrido, or isoxazolo); said phenyl and heteroaryl may each have 1 or2 substituent groups selected,from the class consisting of (C1-6)alkyl, (C1-6) alkoxy, and halogen; R2 and R3 independently represent hydrogen, (C1-6)alkoxy, or (C1-6)alkyl may have 1-3 substituent groups selected from fluorine, benzyloxy, hydroxy, phenyl, benzyl, halogen, nitro, cyano, CO2R4, CONHR4, NR4R5, NR4COR5, and SOpCH2Ph (where p represents 0, 1, or 2); or R2 and R3 may jointly and in combination with the adjacent carbon atom form a 5- or 6-membered ring (where the ring atoms are selected from the class consisting of carbon, nitrogen, and oxygen; e.g. methylenedioxy, ethylenedioxy, or a lactam, ring); R4 and R5 independently represent hydrogen or (C1-6)alkyl, or R4 and R5 of NR4R5 may jointly and in, combination with the adjacent nitrogen form a 4- through 8-membered ring containing at least one nitrogen atom (the other ring atoms are carbon and oxygen and/or nitrogen); R4 and R5 of NR4COR5 may jointly and in combination with the adjacent nitrogen and carbon atoms form a 4- through 8-membered lactam ring; X represents nitrogen or CH; Y represents oxygen, sulfur, or NR6; R6 represents hydrogen, (C1-6)alkyl, CO(C1-6)alkyl, or SO2-phenyl (the phenyl may have 1 to 5 substituent groups independently selected from among (C1-4)alkyl species); n represents an integer of 1 through 4; q in n occurrences independently represents 1 or 2; z represents oxygen or sulfur. The following compound is typically disclosed as a cholinesterase inhibitor: 
EP 560235 discloses a fused heterocyclic ketone derivative of the following formula or its salt as a cholinesterase inhibitor: 
wherein R1 represents hydrogen, a hydrocarbon group which may be substituted, or an acyl group which may be substituted; ring A represents a benzene ring which may be further substituted; n represents an integer of 1 through 10; R2, R3, and R4 may be the same or different and each represents hydrogen or a hydrocarbon group which may be substituted; R3 and R4 may jointly and in combination with the adjacent nitrogen atom form a heterocyclic group which may be substituted; R2 may not be the same in n occurrences; k represents an integer of 0 to 3; m represents an integer of 1 to 8; provided, however, that when k=0 and m=2, n greater than 1. Specifically, the compound of the following formula is disclosed as a cholinesterase inhibitor: 
EP 562832 discloses a compound of the formula: 
wherein R1 and R2 independently represent hydrogen or an organic group; p represents 0, 1, 2, or 3; U represents xe2x80x94COxe2x80x94 or xe2x80x94CH(OR3)xe2x80x94 (where R3 represents hydrogen or a hydroxy-protecting group); V represents an aliphatic hydrocarbon group which may be unsaturated; W represents a nitrogen-containing group. Specifically, the compound of the following formula is mentioned as a cholinesterase inhibitor: 
Japanese Patent Unexamined Publication No. 169569/1990 discloses acyclic amine derivative of the following formula or a pharmacologically acceptable salt thereof: 
where J represents,
(a) (1) phenyl, (2) pyridyl, (3) pyrazyl, (4) quinolyl, (5) cyclohexyl, (6) quinoxalyl, or (7) furyl, each substituted or unsubstituted,
(b) a univalent or bivalent group, the phenyl moiety of which may be substituted, which is selected from the class consisting of (1) indanyl, (2) indanonyl, (3), indenyl, (4) indenonyl, (5) indandionyl, (6) tetralonyl, (7) benzosuberonyl, (8) indanolyl, (9) a group of the formula: 
(c) a univalent group derived from a cyclic amide compound,
(d) a lower alkyl group, or
(e) a group of the formula R1xe2x80x94CHxe2x95x90CHxe2x80x94 (where R1 represents hydrogen or lower alkoxycarbonyl);
B represents a group of the formula xe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94COxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94NR2xe2x80x94(C(R2)H)nxe2x80x94 (where R2 represents hydrogen, lower alkyl, acyl, lower alkylsulfonyl, phenyl which may be substituted, or benzyl), a group of the formula xe2x80x94COxe2x80x94NR4xe2x80x94(C(R2)H)nxe2x80x94 (where R4 represents hydrogen, lower alkyl, or phenyl), a group of the formula xe2x80x94CHxe2x95x90CHxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94Oxe2x80x94COOxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94Oxe2x80x94COxe2x80x94NHxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94NHxe2x80x94COxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94CH2xe2x80x94COxe2x80x94NHxe2x80x94((R2)H)nxe2x80x94, a group of the formula xe2x80x94COxe2x80x94NHxe2x80x94(C(R2)H)nxe2x80x94, a group of the formula xe2x80x94C(OH)Hxe2x80x94(C(R2)H)nxe2x80x94 (in each of the above formulas, n represents an integer of 0-10; R2 represents hydrogen or methyl in the sense that the alkylene group of the formula xe2x80x94(C(R2)H)nxe2x80x94 is either unsubstituted or substituted by one or more than one methyl group), a group of the formula xe2x95x90(CHxe2x80x94CHxe2x95x90CH)bxe2x80x94 (where b represents an integer of 1 to 3), a group of the formula xe2x95x90CHxe2x80x94(CH2)cxe2x80x94 (where c represents an integer of 0 or 1 to 9), a group of the formula xe2x95x90(CHxe2x80x94CH)dxe2x95x90 (where d represents an integer of 0 or 1-5), a group of the formula xe2x95x90COxe2x80x94CHxe2x95x90CHxe2x80x94CH2xe2x80x94, a group of the formula xe2x80x94COxe2x80x94CH2xe2x80x94C(OH)Hxe2x80x94CH2xe2x80x94, a group of the formula xe2x80x94C(CH3)Hxe2x80x94COxe2x80x94NHxe2x80x94CH2xe2x80x94, a group of the formula xe2x80x94CHxe2x95x90CHxe2x80x94COxe2x80x94NHxe2x80x94(CH2)2xe2x80x94, a group of the formula xe2x80x94NHxe2x80x94, a group of the formula xe2x80x94Oxe2x80x94, a group of the formula xe2x80x94Sxe2x80x94, a dialkylaminoalkylcarbonyl group, or a lower alkoxycarbonyl group;
T represents nitrogen or carbon;
Q represents nitrogen, carbon or a group of the formula:  greater than N(copyright)O;
K represents hydrogen, substituted or unsubstituted phenyl, arylalkyl, the phenyl moiety of which may be substituted, cinnamyl, the phenyl moiety of which may be substituted, lower alkyl, pyridylmethyl, cycloalkylalkyl, adamantanemethyl, furylmethyl, cycloalkyl, lower alkoxycarbonyl, or acyl;
q represents an integer of 1 to 3;

in the formula represents a single bond or a double bond. Specifically, the following compound is typically disclosed as a cholinesterase inhibitor: 
U.S. Pat. No. 5,106,856 discloses a compound of the formula: 
wherein X represents hydrogen, hydroxy, nitro, lower alkyl, or lower alkoxy; Y represents hydrogen or lower alkoxy, or X and Y jointly form OCH2O. Specifically, the following compound is disclosed as a cholinesterase inhibitor: 
Japanese Patent Unexamined Publication No. 22333/1979 discloses a compound of the following formula as a synthetic intermediate of base thioether compounds having antifungal, antibacterial and antiinflammatory activities:
Rxe2x80x94COxe2x80x94CHR4xe2x80x94R7
wherein R represents 2-dibenzothienyl, for instance; R4 represents H, for instance; R7 represents xe2x80x94(CH2)nxe2x80x94Z (where n represents 1, 2, or 3; Z represents xe2x80x94NR1R2 (R1 and R2 independently represent H or C1-4 alkyl or jointly represent C4-7 alkylene or 3-oxapentamethylene), for instance.
Japanese Patent Unexamined Publication No. 167546/1984 discloses a compound of the formula: 
wherein Ar typically represents 
(Z represents a direct bond, xe2x80x94CH2xe2x80x94, xe2x80x94CH2CH2xe2x80x94, or xe2x80x94Oxe2x80x94);
X represents an amino group of the formula xe2x80x94N(R11)(R12) where
R11represents hydrogen, C1-12 alkyl, C2-4 alkyl substituted by one or more members selected from the following class: OH, C1-4 alkoxy, CN, and xe2x80x94COO (C1-4 alkly), or C3-5 alkenyl, cyclohexyl, C7-9 phenylalkyl, phenyl, or phenyl substituted by C1, C1-4 alkyl, OH, C1-4 alkoxy, or xe2x80x94COO(C1-4 alkyl); or R11 and R1 taken together represent xe2x80x94CH2OCH2xe2x80x94;
R12 has one of the meanings given to R11 or, taken, together with R11, represents a C5-7 alkylene group or a C3-7 alkylene group interrupted by xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, or xe2x80x94N(R14)xe2x80x94 or, taken together with R2, represents C1-8 alkylene, C7-10 phenylalkylene, C2-4 oxyalkylene, or azaalkylene;
R1 and R2 independently represent C1-8 alkyl.
Specifically, the compound of the following formula is disclosed as a photocurable color composition: 
EP-A-0378207 discloses a cyclic amine compound of the following formula or a salt thereof: 
wherein B represents a saturated or unsaturated 5- through 7-membered aza-heterocyclic group which may be substituted; A represents a bond or an alkylene or alkenylene group which may be substituted by a hydrocarbon residue, oxo, or hydroxy;

represents a single bond or a double bond (however, when A represents a bond,

represents a single bond);
R2 and R3 independently represent hydrogen or a hydrocarbon residue which may be substituted (provided, however, that both R2 and R3 do not concurrently represent hydrogen) or may jointly and in combination with the adjacent nitrogen atom form a cycloamino group; n represents 0, 1, or 2; and p represents 1 or 2. Specifically the following compound, among others, is mentioned as a cholinesterase inhibitor: 
Japanese Patent Unexamined Publication No. 206875/1994 discloses a cholinesterase inhibitor characterized by comprising a heterocyclic compound of the following formula or a salt thereof: 
wherein ring A represents a benzene ring which may be further substituted; ring B represents a nonaromatic hetero ring containing 2 or more hetero atoms, which may be the same or different, as ring members, which may be substituted; R1 represents hydrogen or a hydroctarbon group which may be substituted and may not be the same in n occurrences; Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted; n represents an integer of 1 through 10. Specifically, the following compound, for instance, is described: 
Japanese Patent Unexamined Publication No. 206854/1995 discloses a tricyclic fused heterocyclic derivative of the following formula or a salt thereof: 
where Ar represents a tricyclic benzenoid system including at least one hetero ring, which system may optionally be substituted; n represents an integer of 2 through 10; R1 represents hydrogen or a hydrocarbon group which may be substituted; R1 may not be the same in n occurrences; Y represents, as each unsubstituted or substituted, 4-piperidinyl, 1-piperazinyl, or 4-benzyl-1-piperidinyl. Specifically, the compound of the following formula is mentioned as a cholinesterase inhibitor: 
Japanese Patent Unexamined Publication No. 309835/1995 discloses a tetracyclic fused hetero system of the following formula or a salt thereof. 
wherein Ar represents a tetracyclic fused hetero system which may be substituted; n represents an integer of 1 through 10; R1 represents hydrogen or A hydrocarbon group which may be substituted; R1 may not be the same in n occurrences; Y means an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted. Typically, the compound of the following formula is mentioned as a cholinesterase inhibitor: 
WO 910 3243 discloses a compound of the following formula or a pharmaceutically acceptable salt thereof, which finds application as an antipsychotic drug: 
wherein m represents 0 through 3; n represents 0 through 3; both of m and n do not concurrently represent 0; p represents 0 through 3; X represents 0, S, SO, SO2, NR6, CR7R8, CO, or CHOH; R1, R3, and R7 independently represent hydrogen, C1-5 alkyl, halogen, NR10R11, OH, COOH, C2-6 carboalkoxy, CN, Ar, C1-5 alkoxy, or C1-5alkylthio; R2, R4, and R8 independently represent hydrogen, C1-5 alkyl, C2-6 carboalkoxy, CN, C1-5 alkoxy, or Ar1; when X represents O, S, SO, SO2, or NR6, R1, R2, R3, and r4 are not C1-5 alkoxy, C1-5 alkylthio, NR10R11, or OH; R5 represents hydrogen, alkyl, halogen, OH, or alkenyl; R6 represents hydrogen, C1-5 alkyl, or Ar1; Ar and Ar1 respectively represent naphthyl, pyridyl, pirimidyl, indolyl, quinolinyl, isoquinolinyl, or phenyl, each substituted or unsubstituted, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl as substituted by 1-7 halogen atoms, SH, S(O)txe2x80x94C1-3 alkyl (t=1, 2, or 3), C2-6 dialkylamino, halogen, C1-3 alkylamino, NH2, CN, NO2, SO3H, tetraz-ole, COOH, C2-6 carbalkoxy, CONH2, SO2NO2, COR9, CONR12R13, SO2NR12R13, Ar2, OAr2, or SAr2; Ar2 represents naphthyl or phenyl, which may be substituted by C1-3 alkyl, C1-3 haloalkyl as substituted by 1 to 7 halogen atoms, C1-3 alkoxy, halogen, or C1-3 alkylthio; R9, R10, R11, R12, and R13 respectively represent hydrogen, C1-5 alkyl, or phenyl; R10 and R11 may jointly form a C3-6alkylene chain; R12 and R13 may jointly form a C3-6 alkylene chain; a or b represents a double bond or a single bond and both a and b do not concurrently represent a double bond.
It is disclosed in Khim.-Farm. Zh. 21, 569, 1987 that a compound of the following general formula has antiinflammatory activity: 
wherein R=Ac, COEt, COPr, COCHMe2, CO(CH2)2Cl, CO(CH2)3Cl, COCH2NMe2, CO(CH2)2NMe2, CO(CH2)3NMe2, all inclusive of salts thereof, or Rxe2x95x90COCHxe2x95x90CHPh; Xxe2x95x90CH2 or O; n=1, 2, or 3.
It is mentioned in Chemical Abstracts, 89, 36594y, 1978 that a compound of the following general formula has anticonvulsant, arterial blood pressure-lowering, and local anesthetic actions: 
wherein R1=H, Me; n=2, 3.
It is reported in Journal of the Pharmaceutical Society of Japan, 97, 540, 1977 that a compound of the following general formula has antidepressant activity: 
wherein R1=H, Me; R2=H, Cl, Me; R3=H, F, Me, OMe, Cl; n=1, 2, 3; Z=O, OH, H (Compound (I)) or R2=H, Cl; R4=H, Me; NR52=NMe2, morpholino, or piperidino (Compound (II)).
EP 163537 mentions that a compound of the following general formula has muscle relaxant activity: 
wherein R=4-cycloalkylphenyl, 3,4-methylenedioxyphenyl, 2,3-dihydro-5-benzofuranyl; R1=alkyl, cycloalkyl, cyclopentylmethyl; R2=substituted or unsubstituted pyrrolidino, piperidino, hexahydro-1H-azepin-1-yl, octahydro-1-azocinyl.
It is reported in Chemical Abstracts 91, 211631y, 1979 that a compound of the following formula was synthesized as a derivative of the alkaloid cytisine and that this derivative was found to have anticholinergic activity: 
wherein Rxe2x95x90H, Me
Helvetica Chimica Acta, 51, 1616, 1968 describes compounds of the following formula (A) and formula (B) as synthetic intermediates of the sympathomimetic alkanolamine of the following formula (C): 
Japanese Patent Unexamined Publication No. 97952/1977 describes a synthetic intermediate for the production of an aminoalcohol derivative having antihypertensive, anticonvulsant, vasodilative, and sedative activities; said aminoalcohol derivative having the formula: 
wherein R1=H, alkyl, phenyl; R2=C1-3 alkyl; R3=alkenyl, alkinyl, cycloalkyl, alkyl; R4=H, alkyl; NR3R4=morpholino, pyrrolidino, piperidino; R5=H, C1-3 alkyl; R6=H, acyl; n=1 through 3; X=S, O, NH; Y=CH2, S, and said synthetic intermediate being represented by the following formula: 
wherein the respective symbols have the same meanings as defined above.
It is disclosed in Japanese Patent Unexamined. Publication No. 7158/1984 that a 1,5-benzodioxepine derivative of the following formula and its acid addition salt have vasodepress or antihypertensive activity: 
wherein R1 represents hydrogen or C1-3 alkyl; R2 represents C1-3 alkyl; X represents xe2x80x94CH(OH)xe2x80x94 or 
Ar represents 
wherein Y represents hydrogen, xe2x80x94OCH3, halogen, or 
n represents an integer of 1 through 5.
FR-M3635 discloses a compound of the following formula: 
as a synthetic intermediate of the sympathomimetic 1,4-benzodioxane of the formula: 
Furthermore, Chemical Abstracts, 67, 54087k (1967), 68, 105121x (1968), 75, 88548s (1971), and 76, 153682t (1972) describe processes for synthesis of 1,4-benzodioxane derivatives of the formula: 
wherein 
represents an amino group which may be substituted or a cycloamino group which may be substituted; p represents 1 or 2. However, none of those literature contains teachings about the biological activity or pharmacological activity of the compounds.
The demand exists for development of a prophylactic and/or treating drug for obesity and obesity-associated disease which should have a reduced risk for adverse effects on the central nervous system and could be more universally administered than the known antiobesity compounds.
In view of the above state of the art, the inventors of the present invention explored for new thermogenic and antiobesity substances having no central side effects with due diligence and discovered that, regardless of the kinds of substituent groups that may be present, a structurally unique aminoketone, derivative of the following formula (I): 
wherein Ar represents a phenyl group which may be substituted and/or condensed; n represents an integer of 1 to 10; R represents hydrogen atom or a hydrocarbon group which may be substituted, which may not be the same in n occurrences; R may be bound to either Ar or a substituent or Ar; Y represents an amino group which may be subsituted or a nitrogen-containing saturated heterocyclic group which may be substituted or its salt, has surprisingly high thermogenesisa accelerating activity, lipolysis accelerating activity, intraadipocellular cAMP concentration-increasing activity, and a prophylactic and treating effect on obesity and obesity-associated diseases. The present invention has been developed on the basis of the above findings.
The present invention, therefore, relates to:
(1) A thermogenic composition comprising a compound of the formula: 
xe2x80x83wherein Ar represents an optionally condensed phenyl group which may be substituted; n represents an integer of 1 to 10; R represents a hydrogen atom or a hydrocarbon group which may be substituted, which may not be the same in n occurrences; R may be bound to either Ar or a substituent on Ar; Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof,
(2) A thermogenic composition according to (1), wherein Ar represents a group of the formula: 
xe2x80x83wherein R1 represents a hydrogen atom, a hydrocarbon group which may, be substituted, an acyl group, or a heterocyclic group which may be substituted; ring A represents a benzene ring which may be substituted; ring Bxe2x80x2 represents a 5- to 9-membered nitrogen-containing heterocyclic ring which may be substituted by oxo,
(3) A thermogenic composition according to (1), wherein Ar represents a group of the formula: 
wherein king A represents a benzene ring which may be substituted; ring Cxe2x80x2, ring Dxe2x80x2, ring Exe2x80x2, king Fxe2x80x2 and ring Gxe2x80x2 independently represent a 5- to 9-membered nitrogen-containing heterocyclic king which may be substituted by oxo; ring D, ring F and ring G independently represent a ring which may be substituted; R1 represents a hydrogen atom, a hydrocarbon group which may be substituted, an acyl group, or, a heterocyclic group which may be substituted,
(4) The thermogenic composition according to (1), wherein Ar represents a group of the formula: 
xe2x80x83wherein R1 represents a hydrogen atom, a hydrocarbon group which may be substituted, an acyl group, or a heterocyclic group which may be substituted,
(5) A thermogenic composition according to (1), wherein R represents a hydrogen atom,
(6) A thermogenic composition according to (1), wherein Y represents a group of the formula: 
xe2x80x83wherein R6 represents (i)a phenyl-C1-6 alkyl group which may be substituted by C1-6 alkyl which may be substituted, C1-6 alkoxy which may be substituted, halogen, nitro, mono- or di-C1-6 alkyl-carbamoyloxy, hydroxy, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclic aminocarbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkylsulfonylamino, amidino which may be substituted, ureido which may be substituted, sulfo, or heterocyclic group which may be substituted, (ii)a hydrogen atom, (iii)a C1-6 alkyl group which may be substituted by halogen, hydroxy, C16 alkoxy, amino, mono- or di-C1-6 alkylamino, carboxyl, cyano, heterocyclic group which may be substituted, or C1-6 alkoxy-carbonyl, (iv)a C1-6alkyl-carbonyl group which may be substituted by mono- or di-C1-6 alkylamino, or C1-6alkoxy-carbonyl, (v)a benzoyl group which may be substituted, (vi)a C1-6 alkylsulfonyl group, (vii)an aminocarbonyl group which may be substituted, (viii)a C1-6 alkoxy-carbonyl group, (ix)a fluorenyl group which may be substituted, or (x)a naphthyl-C1-6alkyl group which may be substituted,
(7) A thermogenic composition according to (1), wherein Y represents a 1-benzyl-4-piperidinyl group, a 4-benzyl-1-piperazinyl group or a 4-benzyl-1-piperidinyl group, each benzyl of which may be substituted respectively,
(8) A thermogenic composition according to (1), wherein n represents an integer of 1 to 6,
(9) A thermogenic composition according to (1), wherein R represents a hydrogen atom, n represents 2, and Y represents a 1-benzyl-4-piperidinyl group,
(10) A thermogenic composition according to (1), comprising a compound of the formula: 
xe2x80x83wherein R1 represents a hydrogen atom, a hydrocarbon group which may be substituted, an acyl group, or a heterocyclic group which may be substituted; Yxe2x80x2 represents a 4-piperidinyl group in which nitrogen may be substituted; n represents an integer of 3 to 6, or a salt thereof,
(11) A thermogenic composition according to (1), comprising a compound of the formula: 
xe2x80x83wherein the symbols are as defined in (10), or a salt thereof,
(12) A thermogenic composition according to (1), comprising a compound of the formula: 
xe2x80x83wherein the symbols are As defined in (10), or a salt thereof,
(13) A thermogenic composition according to (1), which, is for an antiobese agent,
(14) A thermogenic composition according to (1), which is for a lipolytic agent,
(15) A thermogenic composition according to (1), which is for a prophylactic and/or treating agent for obesity-associated disease or diabetes,
(16) A compound of the formula: 
xe2x80x83wherein the symbols are as defined in (10), or a salt thereof,
(17) A compound according to (16), wherein the substituent on a hydrocarbon group and a heterocyclic group, defined as R1, is selected from the group consisting of halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkyl-amino, di-lower alkyl-amino, 5- to 7-membered cyclic amino-which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, and heterocyclic group which may be substituted,
(18) A compound of the formula: 
xe2x80x83wherein the symbols are as defined in (10), or a salt thereof,
(19) A compound according to (18), wherein the substituent on a hydrocarbon group and a heterocyclic group, defined as R1, is selected from the group consisting of halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkyl-amino, di-lower alkyl-amino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, and heterocyclic group which may be substituted,
(20) A compound of the formula: 
xe2x80x83wherein the symbols are as defined in (10),
(21) A compound according to (20), wherein the substituent on a hydrocarbon group and a heterocyclic group, defined as R1, is selected from the group consisting of halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkyl-amino, di-lower alkyl-amino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, and heterocyclic group which may be substituted,
(22) A compound according to (16), wherein R1 represents a C1-6 alkyl group or a C7-16 aralkyl group, each of which may be substituted respectively,
(23) A compound according to (22), wherein the substituent on a C1-6 alkyl group or a C7-16 aralkyl, group, defined as R1, is selected from the group consisting of halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl,cyclicamino-carbonyl which may be substituted, amino, mono-lower alkyl-amino, di-lower alkyl-amino, 5- to 7-membered cyclic amino which may contain 1 to-3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, and heterocyclic group which may be substituted,
(24) A compound according to (16); wherein R1 represents a phenyl-C1-4 alkyl group which may be substituted,
(25) A compound according to (24), wherein the substituent on a phenyl-C1-4 alkyl group, defined as R1, is selected from the group consisting of halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, and heterocyclic group which may be substituted,
(26) A compound according to (16), wherein R1 represents a benzyl group which may be substituted, the substitutent being selected from the group consisting of C1-4 alkyl, trihalogeno-C1-4 alkyl, halogen, nitro, cyano, C1-4 alkoxy, trihalogeno-C1-4 alkoxy, carbamoyl, (4-C1-4 alkyl (e.g. methyl, etc.)-1-piperazinyl)carbonyl, aminothiocarbonyl, carboxyl, C1-4 alkoxy-carbonyl, C1-4 alkoxy-carbonyl-C1-4 alkoxy, carboxyl-C1-4 alkoxy, C1-4 alkoxy-carbonyl-C1-6 alkyl, carboxyl-C1-6 alkyl, amino, acetylamino, C1-4 alkylsulfonylamino, (4-C1-4 alkylphenyl)sulfonylamino, ureido, 3-C1-4 alkyl-ureido, amidino, dihydrothiazolyl, and dihydroimidazolyl,
(27) A compound according to (16), wherein R1 represents a benzyl group which may be substituted, the substitutent being selected from the group consisting of C1-4 alkyl, trihalogeno-C1-4 alkyl, halogen, nitro, cyano, carbamoyl, C1-4 alkoxycarbonyl, C1-4 alkoxycarbonyl-C1-4 alkoxy, amino, acetylamino, C1-4 alkylsulfonylamino, 3-C1-4 alkyl-ureido, amidino and dihydroimidazolyl,
(28) A compound according to (16), wherein Yxe2x80x2 represents the formula: 
xe2x80x83wherein R6 represents (i)a phenyl-C1-6 alkyl group which may be substituted, the substitutent being selected from the group consisting of C1-6 alkyl which may be substituted, C1-6 alkoxy which may be substituted, halogen, nitro, mono- or di-C1-6 alkyl-carbamoyloxy, hydroxy, cyano, carboxyl, C-1-6 alkoxy-carbonyl, carbamoyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, or heterocyclic group which may be substituted, (ii)a hydrogen atom, (iii)a C1-6 alkyl group which may be substituted, the substitutent being selected from the group consisting of halogen, hydroxy, C1-6 alkoxy, amino, mono- or di-C1-6 alkylamino, carboxyl, cyano and C1-6 alkoxy-carbonyl, or (iv)a C1-6 alkyl-carbonyl group which may be substituted by mono- or di-C1-6 alkyl-amino, or C1-6 alkoxy-carbonyl,
(29) A compound according to (28), wherein R6 represents a benzyl group which may be substituted, the substitutent being selected from the group consisting of C1-4 alkyl, trihalogeno-C1-4 alkyl, halogen, nitro, cyano, C1-4 alkoxy, hydroxy, carbamoyl, (4-C1-4 alkylpiperazinyl)carbonyl, morpholinocarbonyl, carboxyl, C1-4 alkoxy-carbonyl, C1-4 alkoxy-carbonyl-C1-4 alkoxy, carboxyl-C1-4 alkoxy, C1-4 alkoxy-carbonyl-C1-6 alkyl, carboxyl-C1-6 alkyl, amino, acetylamino, C1-4 alkylsulfonylamino, (4-C1-4 alkyl-phenyl)sulfonylamino, ureido, 3-C1-4 alkylureido, amidino, dihydrothiazolyl, and dihydroimidazolyl,
(30) A compound according to (28), wherein R6 represents a benzyl group which may be substituted, the substitutent being selected from the group consisting of C1-4 alkyl, trihalogeno-C1-4 alkyl, halogen, nitro, hydroxy, carbamoyl, amino, amidino and dihydroimidazolyl,
(31) A compound according to (16), wherein n represents an integer of 3,4 or 5,
(32) 3-(1-acetyl-4-piperidinyl)-1-[3-(phenylmethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-propanone or salts thereof,
(33) A compound according to (16), which is 4-[1-[(2-methylphenyl)methyl]-4-piperidinyl]-1-[3-[(2-methylphenyl)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-butanone or salts thereof,
(34) A compound according to (16), which is 4-[1-[(3-chlorophenyl)methyl]-4-piperidinyl]-1-[3-[(2-methylphenyl)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-butanone or salts thereof,
(35) 3-[1-[(2-fluorophenyl)methyl]-4-piperidinyl]-1-[4-(phenylmethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-1-propanone or salts thereof,
(36) 1-[4-(phenylmethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-3-[1-[(3,4,5-trimethoxyphenyl)methyl]-4-piperidinyl]-1-propanone or salts thereof,
(37) 3-[1-(phenylmethyl)-4-piperidinyl]-1-[2-(phenylmethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl]-1-propanone or salt thereof,
(38) A compound according to (18), which is ethyl 2-methyl-2-[3-[[4-[4-[2-[(2-methylphenyl)methyl]-2,3,4,5-tetrahydro-1H-2-benzazepin-8-yl]-4-oxobutyl]-1-piperidinyl]methyl]phenyl]propionate or salt thereof,
(39) A compound according to (16), which is 4-[1-[(2-chlorophenyl)methyl]-4-piperidinyl]-1-[3-[(2-methylphenyl)methyl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-butanone or salt thereof,
(40) 1-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3-[1-(phenylmethyl)-4-piperidinyl]-1-propanone or salt thereof,
(41) A method of producing a compound of the formula: 
xe2x80x83wherein R1 is as defined in (10); n represents an integer of 3 to 6; Wa represents a protective group for the N atom or a hydrogen atom, or a salt thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein R1 is as defined above, or salt thereof, with a compound of the formula: 
xe2x80x83wherein Z1 represents a leaving group; W represents a protective group; n is as defined above, or salt thereof, if necessary, followed by deprotectioning reaction,
(42) A method of producing a compound according to
(28), which comprises reacting a compound of the formula: 
xe2x80x83wherein the symbols are as defined in (41), or a salt thereof, with a compound of the formula:
xe2x80x83R6axe2x80x94Z1a
wherein R6a represents (i)a phenyl-C1-6 alkyl group which may be substituted, the substitutent being selected from the group consisting of C1-6 alkyl which may be substituted, C1-6 alkoxy which may be substituted, halogen, nitro, mono- or di-C1-6, alkyl-carbamoyloxy, hydroxy, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkyl-sulfonylamino, amidino which may be substituted, ureido which may be substituted, or heterocyclic group which may be substituted, (ii)a C1-6 alkyl group which may be substituted, the substitutent being selected from the group consisting of halogen, hydroxy, C1-6 alkoxy, amino, mono- or di-C1-6 alkylamino carboxyl, cyano and C1-6 alkoxy-carbonyl, or (iv)a C1-6 alkyl-carbonyl group which may be substituted by mono- or di-C1-6 alkyl-amino, or C1-6 alkoxy-carbonyl; Z1a represents a leaving group, or salt thereof,
(43) A method of producing a compound of the formula: 
xe2x80x83wherein R1a represents a hydrocarbon group which may be substituted, or an acyl group; n is as defined in (41); R6 is as defined in (28), or thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein the symbols ate as defined above or salt thereof, with a compound of the formula:
R1axe2x80x94Z1a
xe2x80x83wherein R1a is as defined above; and Z1a represents a leaving group, or salt thereof,
(44) A pharmaceutical composition which comprises the compound according to (16), and
(45) Use of a compound of the formula: 
xe2x80x83wherein Ar represents an optionally condensed phenyl group which may be substituted; n represents an integer of 1 to 10; R represents a hydrogen atom or a hydrocarbon group which may be substituted, which may not be the same in n occurrences; R may be bound to either Ar or a substituent on Ar; Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof, for preparering a composition for thermogenic, antiobese or lipolytic agent, or prophylactic and/or treating agent for obesity-associated disease or diabetes.
In the above formula, Ar represents xe2x80x9ca phenyl group which may be substituted and/or condensed (forming a fused ring system)xe2x80x9d.
The xe2x80x9csubstituentxe2x80x9d for the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d includes but is not limited to (i) a lower alkyl group which may a halogenated, (ii) a halogen atom(e.g. fluorine, chlorine, bromine, iodine etc.), (iii) a lower akylenedioxy group (e.g. a C1-3 alkylenedioxy group such as methylenedioxy, ethylenedioxy, etc.), (iv) nitror group, (V) cyano group, (vi) hydroxy group, (vii) a lower alkoxy group which may be halogenated, (viii) a lower cycloalky group (e.g. a C3-6 cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), (ix) a lower alkylthio group which may be halogenated, (x) an amino group, (xi) a mono- lower alkylamino group(e.g. a mono-C1-6 alkylamino group such as methylamiano, ethylamino, propylamino, etc.), (xii) a di-lower alkylamino group (e.g. a di-C1-6 alkylamino group such as dimethylamino, diethylamino, etc.), (xiii) a 5- to 7-membered cycloamino group which may have 1 to 3 hetero atoms selected from the group consisting of nitrogen atom, oxygen atom, and sulfur atom in addition to one nitrogen atom (e.g. pyrroligdino, piperidino, piperazino, morpholino, thiomorpholino, etc.), (xiv) a lower alkyl-carbonylamino (e.g. a C1-6 alkyl-carbonylamino group such as acetylamino, propionylamino, butyrylamino, etc.), (xv) an aminocarbonyloxy group, (xvi) a mono- lower alkylamino-carbonyloxy group (e.g. mono-C1-6alkylamino-carbonyloxy such as methylaminocarbonyloxy, ethylaminocarbonyloxy, etc.), (xvii) a di-lower alkylamino-carbonyloxy group (e.g. a di-C1-6 alkylamino-carbonyloxy group such as dimethylaminocarbonyloxy, diethylaminocarbonyloxy, etc.), (xviii) a lower alkylsulfonylamino group (e.g. a C1-6 alkylsulfonylamino group such as methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, etc.), (xix) a lower alkoxy-carbonyl group (e.g. a C1-6 alkoxy-carbonyl group such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isobutoxycarbonyl, etc.), (xx) carboxyl group, (xxi) a lower alkyl-carbonyl group (e.g. a C1-6 alkyl-carbonyl group such as methylcarbonyl, ethylcarbonyl, butylcarbonyl, etc.), (xxii) a lower cycloalkyl-carbonyl group (a C3-6 cycloalkyl-carbonyl group such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc.), (xxiii) a carbamoyl group, (xxiv) a mono-lower alkyl-carbamoyl group (e.g. a mono-C1-6 alkyl-carbamoyl group such as methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, butylcarbamoyl, etc.), (xxv) a di-lower alkyl-carbamoyl group (e.g. a di-C1-6 alkyl-carbamoyl group such as diethylcarbamoyl, dibutylcarbamoyl, etc.), (xxvi) a lower alkylsulfonyl group (e.g. a C1-6 alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.), (xxvii) a lower cycloalkylsulfonyl group (e.g. C3-6 cycloalkylsulfonyl such as cyclopentylsulfonyl, cyclohexylsulfonyl, etc.), (xxviii) a phenyl group, (xxix) a naphthyl group, (xxx) a monophenyl-lower alkyl group (e.g. a mono-phenyl-C1-6 alkyl group such as benzyl, phenylethyl, etc.), (xxxi) a diphenyl-lower alkyl group (e.g. a diphenyl-C1-6 alkyl group such as diphenylmethyl, diphenylethyl, etc.), (xxxii) a monophenyl-lower alkyl-carbonyloxy group (e.g. a monophenyl-C1-6 alkyl-carbonyloxy group such as phenylmethylcarbonyloxy, phenylethylcarbonyloxy, etc.), (xxxiii) a diphenyl-lower alkyl-carbonyloxy group (e.g. a diphenyl-C1-6 alkyl-carbonyloxy group such as diphenylmethylcarbonyloxy, diphenylethylcarbonyloxy, etc.), (xxxiv) a phenoxy group, (xxxv) a monophenyl-lower alkyl-carbonyl group (e.g. a monophenyl-C6 alkyl-carbonyl group such as phenylmethylcarbonyl, phenylethylcarbonyl, etc.), (xxxvi) a diphenyl-lower alkyl-carbonyl group (e.g. a diphenyl-C1-6 alkyl-carbonyl group such as diphenylmethylcarbonyl, diphenylethylcarbonyl, etc.), (xxxvii) a benzoyl group, (xxxviii) a phenoxycarbonyl group, (xxxix) a phenyl-lower alkyl-carbamoyl group (e.g. a phenyl-C1-6 alkyl-carbamoyl group such as phenylmethylcarbamoyl, phenylethylcarbamoyl, etc.), (xxxx) a phenylcarbamoyl group, (xxxxi) a phenyl-lower alkyl-carbonylamino group (e.g. a phenyl-C1-6 alkyl-carbonylamino group such as phenyl-methylcarbonylamino, phenylethylcarbonylamino, etc.), (xxxxii) a phenyl-lower alkylamino group (e.g. a phenyl-C1-6 alkylamino group such as phenyl-methylamino, phenyl-ethylamino, etc.), (xxxxiii) a phenyl-lower alkylsulfonyl group (e.g. a phenyl-C1-6 alkyl-sulfonyl group such as phenylmethylsulfonyl, phenylethylsulfonyl, etc.), (xxxxiv) a phenylsulfonyl group (xxxxv) a phenyl-lower alkyl-sulfinyl group (e.g. a phenyl-C1-6 alkylsulfinyl group such as phenylmethylsulfinyl, phenylethyisulfinyl, etc.), (xxxxvi) a phenyl-lower alkylsulfonylamino group (e.g. a phenyl-C1-6 alkylsulfonylamino group such as phenylmethylsulfonylamino, phenylethylsulfonylamino, etc.), and (xxxxvii) a phenylsulfonylamino group (the (xxviii) a phenyl group, (xxix) a naphthyl group, (xxx) a monophenyl-lower alkyl group, (xxxi) a diphenyl-lower alkyl group, (xxxii) a monophenyl-lower alkyl-carbonyloxy group, (xxxiii) a diphenyl-lower alkyl-carbonyloxy group, (xxxiv) a phenoxy group, (xxxv) a monophenyl-lower alkyl-carbonyl group, (xxxvi) a diphenyl-lower alkyl-carbonyl group, (xxxvii) a benzoyl group, (xxxviii) a phenoxycarbonyl group, (xxxix) a phenyl-lower alkyl-carbamoyl group, (xxxx) a phenylcarbamoyl group, (xxxxi) a phenyl-lower alkyl-carbonylamino group, (xxxxii) a phenyl-lower alkyl-amino group, (xxxxiii) a phenyl-lower alkyl-sulfonyl group, (xxxxiv) a phenylsulfonyl group, (xxxxv) a phenyl-lower alkyl-sulfinyl group, (xxxxvi) a phenyl-lower alkyl-sulfonylamino group and (xxxxvii) a phenylsulfonylamino group may in turn have 1 to 4 substituent groups selected from the group consisting of, for example, lower alkyl (e.g. C1-6 alkyl such as, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, etc.), lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, propoxy, isopopoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.), halogen (e.g. chlorine, bromine, iodine, etc.), hydroxy, benzyloxy, amino, mono-lower alkyl-amino (e.g. mono-C1-6 alkylamino such as methylamino, ethylamino, propylamino, etc.), di-lower alkyl-amino (e.g. di-C1-6 alkylamino such as dimethylamino, diethylamino, etc.), nitro, lower alkyl-carbonyl (e.g. C1-6 alkyl-carbonyl such as methylcarbonyl, ethylcarbonyl, butylcarbonyl, etc.), and benzoyl), among others.
The above-mentioned xe2x80x9clower alkyl group which may be halogenatedxe2x80x9d includes a lower alkyl group (e.g. a C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, hexyl, etc.) optionally having 1 to 3 halogen atoms (e.g. chlorine, bromine, iodine). Specifically, methyl, chloromethyl, difluoromethyl, trichloromethyl, trifluoromethyl, ethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, propyl, 3,3,3-trifluoropropyl, isopropyl, butyl, 4,4,4-trifluorobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopefntyl, 5,5,5-trifluoropentyl, hekyl, 6,6,6-trifluorohexyl, etc. can be mentioned.
The above-mentioned xe2x80x9clower alkoxy group which may be halogenatedxe2x80x9d includes but is not limited to a lower, alkoxy group (e.g. a C1-6 alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.) optionally having 1 to 3 halogen atoms (e.g. chlorine, bromine, iodine). Specifically, methoxy, difluoromethoxy, trifluoromethoxy, ethoxy, 2,2,2-trifluoroethoxy, n-propoxy, isopropoxy, n-butoxy, 4,4,4-trifluorobutoxy, isobutoxy, sec-butoxy, pentyloxy, hexyloxy, etc. can be mentioned.
The above-mentioned xe2x80x9clower alkylthio group which may be halogenatedxe2x80x9d includes but is not limited to a lower alkkylthio group (e.g. a C1-6 alkylthio group such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, etc.) optionally having 1 to 3 halogen atoms (chlorine, bromine, iodine). Specifically, methylthio, difluoromethylthio, trifluoromethylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, 4,4,4-trifluorobutylthio, isobutylthio, sec-butylthio, tert-butylthio, penthylthio, hexylthio, etc. can be mentioned.
The preferred xe2x80x9csubstituentxe2x80x9d for the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d includes (i) an amino group, (ii) a mono-lower alkylamino group (e.g. a mono-C1-6 alkylamino group such as methylamino, ethylamino, propylamino, etc.), (iii) a di-lower alkylamino group (e.g. a di-C1-6 alkylamino group such as dimethylamino, diethylamino, etc.)i (iv) a 5- to 7-membered cycloamino group which may have 1 to 3 hetero-atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to one nitrogen atom (e.g. pyrrolidino, piperidino, piperazino, morpholino, thiomorpholino, etc.), (v) a lower alkyl-carbonylamino group (e.g. a C1-6 alkyl-carbonylamino group such as acetylamino, propionylamino, butyrylamino, etc.), (vi) an aminocarbonyloxy group, (vii) a mono-lower alkylamino-carbonyloxy group (e.g. a mono-C1-6 alkylamino-carbonyloxy group such as methylaminocarbonyloxy, ethylaminocarbonyloxy, etc.), (viii) a di-lower alkylamino-carbonyloxy group (e.g. a di-C1-6 alkylamino-carbonyloxy group such as dimethylaminocarbonyloxy, diethylaminocarbonyloxy, etc.), (ix) a lower alkylsulfonylamino group (e.g. a C1-6 alkylsulfonylamino group such as methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, etc.), (x) a phenyl-lower alkylamino group (e.g. a phenyl-C1-6 alkylamino group such as phenylmetlhylamino, phenylethylamino, etc.), (xi) a phenyl-lower alkylsulfonylamino group (e.g. a phenyl-C1-6 alkylsulfonylamino group such as phenylmethylsulfonylamino, phenylethylsulfonylamino, etc.), (xii) a phenylsulfonylamino group, (xiii) a halogen atom (e.g. fluorine, chlorine), (xiv) a lower alkyl group which may be halogenated (e.g. methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, etc.), and (xv) a lower akloxy group which may be halogenated (e.g. methoxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethoxy, etc.). Particularly preferred is a 5- to 7-membered cycloamino group optionally having 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to one nitrogen atom (e.g. pyrrolidino, piperidino, piperazino, morpholino, or thiomorpholino etc.).
The manner of condensation of the xe2x80x9cphenyl groupxe2x80x9d of xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d includes but is not limited to:
(1) fusion to a monocyclic hetero ring which may be substituted,
(2) fusion to a bicyclic hetero system which may be substituted or to two similar or dissimilar monocyclic rings (at least one of the two rings is a monocyclic hetero ring), and
(3) fusion to a tricyclic hetero ring which may be substituted.
The group formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a monocyclic hetero ring includes but is not limited to the group of the formula: 
wherein ring B represents a hetero ring which may be substituted; ring A represents a benzene ring which may be substituted.
The substituent for ring A may be the same as the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d.
The xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d, for ring B includes but is not limited to 4- to 14-membered rings, preferably 5- to 9-membered rings, which may be aromatic or nonaromatic. The hetero atom, which may be a nitrogen atom, an oxygen atom, and/or a sulfur atom, may range from 1 to 3 or 4. Thus, for example, pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholinre, pyyrole, pyrazole, 1,2,3-triazole, oxazole, oxazoline, thiazole, thiazoline, isoxazole, imidazoline, etc. can be mentioned. Particularly preferred are 5- to 9-membered nonaromatic hetero rings containing one hetero atom or two similar or dissimilar hetero atoms (e.g. pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, etc.). In particular, nonaromatic hetero rings containing one hetero atom selected from the group consisting a nitrogen atom, an oxygen atom, and a sulfur atom and nonaromatic nitrogen-containing hetero rings containing one hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom in addition to one nitrogen atom can be used with advantage.
The xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chetero ring which may be substitutedxe2x80x9d for ring B may be situated on any ring carbon atom of ring B. The substituent which may thus be present on a ring carbon atom of ring B may range from 1 to 5 in number and can be selected from the group consisting of (i) halogen (e.g. fluorine, chlorine, bromine, iodine), (ii) nitro, (iii) cyano, (iv) oxo, (v) hydroxy, (vi) lower alkyl (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, etc.), (vii) lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, etc.), (viii) lower alkylthio (e.g. C1-6 alkylthio such as methylthio, ethylthio, propylthio, etc.), (ix) amino, (x) mono-lower alkylamino (e.g. mono-C1-6 alkylamino such as methylamino, ethylamino, propylamino, etc.), (xi) di-lower alkylamino (e.g. di-C1-6 alkylamino such as dimethylamino, diethylamino, etc.), (xii) 5- to 7-membered cycloamino which may have 1 to 3 hetero-atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to carbon and one nitrogen atom (e.g. pyrrolidino, piperidino, piperazino, morpholino, thiomorpholino, etc.), (xiii) lower alkyl-carbonylamino (e.g. C1-6 alkyl-carbonylamino such as acetylamino, propionylamino, butyrylamino, etc.), (xiv) lower alkylsulfonylamino (e.g. C1-6 alkylsulfonylamino such as methylsulfonylamino, ethylsulfonylamino, etc.), (xv) lower alkoxy-carbonyl (e.g. C1-6 alkoxy-carbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), (xvi) carboxyl, (xvii) lower alkyl-carbonyl (e.g C1-6 alkyl-carbonyl such as methylcarbonyl, ethylcarbonyl, propylcarbonyl, etc.), (xviii) carbamoyl, (xix) mono-lower alkylcarbamoyl (e.g. mono-C1-6 alkylcarbamoyl such as methylcarbamoyl, ethylcarbamoyl, etc.), (xx) di-lower alkylcarbamoyl (e.g. di-C1-6 alkyl-carbamoyl such as dimethylcarbamoyl, diethylcarbamoyl, etc.), (xxi) lower alkylsulfonyl (e.g. C1-6 alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.).
Particularly preferred are oxo and lower alkyl (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, etc.), oxo being chosen in many instances.
When ring B has a nitrogen atom as a ring member, a substituent may be present on a nitrogen atom. Thus, ring B may have  greater than Nxe2x80x94R1, wherein R1 represents hydrogen atom, a hydrocarbon group which may be substituted, an acyl group, or a heterocyclic group which may be substituted.
The xe2x80x9chydrocarbon groupxe2x80x9d of the xe2x80x9chydrocarbon group which may be substituted for R1 is the group available upon elimination of one hydrogen atom from a hydrocarbon compound, including acyclic (linear) or cyclic hydrocarbon groups such as alkyl, alkenyl, alkinyl, cycloalkyl, aryl, and aralkyl groups. Preferred among such hydrocarbon groups are C1-16 hydrocarbon groups, which may be acyclic, cyclic, or acyclic-cyclic.
The acyclic and cyclic hydrocarbon groups mentioned above include
(1) straight-chain or branched lower alkyl groups (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc.),
(2) straight-chain or branched lower alkenyl groups (e.g. C2-6 alkenyl such as vinyl, allyl, isopropenyl, butenyl, isobutenyl, sec-butenyl, etc.),
(3) straight-chain or branched lower alkynyl groups (e.g. C2-6 alkynyl such as propargyl, ethynyl, butynyl, 1-hexynyl, etc.),
(4) monocyclic lower cycloalkyl groups (e.g. monocyclic C3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.),
(5) bridged cyclic saturated lower hydrocarbon groups (e.g. bridged cyclic saturated C8-14 hydrocarbon groups such as bicyclo[3.2.1]oct-2-yl, bicyclo[3.3.1]non-2-yl, adamantan-1-yl, etc.), and
(6) aryl groups (e.g. C6-14 aryl such as phenyl, 1-naphthyl, 2-naphthyl, biphenyl, 2-indenyl, 2-anthryl, etc.; preferably, phenyl).
The preferred acyclic-cyclic hydrocarbon group mentioned above includes
(1) lower aralkyl groups (e.g. C7-16 aralkyl groups such as phenyl-C1-10 alkyl (e.g. benzyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, etc.), naphthyl-C1-6 alkyl (e.g. a-naphthylmethyl etc.), diphenyl-C1-3 alkyl (e.g. diphenylmethyl, diphenylethyl, etc.), among others),
(2) arylalkenyl groups (e.g. C6-14 aryl-C2-12 alkenyl groups such as phenyl-C2-12 alkenyl (e.g. styryl, cinnamyl, 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, etc.) among others),
(3) aryl-C2-12 alkynyl groups (e.g. C6-14 aryl-C2-12 alkynyl groups such as phenyl-C2-12 alkynyl (e.g. phenylethynyl, 3-phenyl-2-propynyl, 3-phenyl-1-propynyl, etc.) among others),
(4) lower cycloalkyl-lower alkyl groups (e.g. C3-7 cycloalkyl-C1-6 alkyl groups such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cycloheptylpropylbutyl, cyclopropylbutyl, cyclobutylbutyl, cyclopentylbutyl, cyclohexylbutyl, cycloheptylbutyl, cyclopropylpentyl, cyclobutylpentyl, cyclopentylpentyl, cyclohexylpentyl, cycloheptylpentyl, cyclopropylhexyl, cyclobutylhexyl, cyclopentylhexyl, cyclohexylhexyl, etc.),
(5) aryl-aryl groups (e.g. biphenyl etc.), or
(6) aryl-aryl-C1-10 alkyl groups (e.g. biphenylmethyl, biphenylethyl, etc.).
The preferred xe2x80x9chydrocarbon groupxe2x80x9d for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d for R1 includes but is not limited to:
(1) straight-chain, branched or cyclic alkyl group, preferably, straight-chain or branched C1-6 alkyl groups (e.g. C1-6 methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc.), cyclic C3-8 alkyl group (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), straight-chain-branched-cyclic C4-12 alkyl group (e.g. cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclohexylethyl (4-methylhexyl)methyl etc.), and
(2) C7-16 aralkyl groups (e.g. phenyl-C1-10 alkyl (e.g. benzyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, etc.), naphthyl-C1-6 alkyl (e.g. a-naphthylmethly etc.), diphenyl-C1-3 alkyl (e.g. diphenylmethyl, diphenylethyl, etc.), among others); the still more preferred are C7-10 aralkyl groups (e.g. phenyl-C1-4 alkyl such as benzyl, phenylethyl, phenylpropyl, etc.).
The xe2x80x9chydrocarbon groupxe2x80x9d for R1 may be substituted and the substituent that may be present includes groups which are generally used as substituent groups for hydrocarbon groups. The substituent includes but is not limited to: (i) halogen (e.g. fluorine, chlorine, bromine, iodine), (ii) nitro, (iii) cyano, (iv) oxo, (v) hydroxy, (vi) lower alkyl (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, etc.) which may be substituted by phenyl, (vii) lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, etc.) which may be substituted by phenyl, (viii) lower alkylthio (e.g. C1-6 alkylthio such as methylthio, ethylthio, propylthio, etc.) which may be substituted by phenyl, (ix) amino, (x) mono-lower alkylamino (e.g. mono-C1-6 alkylamino such as methylamino, ethylamino, propylamino, etc.), (xi) di-lower alkylamino (e.g. di-C1-6 alkylamino such as dimethylamino, diethylamino, etc.), (xii) 5- to 7-membered cycloamino which may have 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to carbon and one nitrogen atom (e.g. pyrrolidino, piperidino, piperazino, morpholino, thiomorpholino, etc.), (xiii) lower alkyl-carbonylamino (e.g. C1-6-alkyl-carbonylamino such as acetylamino, propionylamino, butyrylamino, etc.), (xiv) lower alkylsulfonylamino (e.g. C1-6 alkylsulfonylamino such as methylsulfonylamino, ethylsulfonylamino, etc.), (xv) lower alkoxy-carbonyl (e.g. C1-6 alkoxy-carbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), (xvi) carboxyl, (xvii) lower alkyl-carbonyl (e.g. C1-6 alkyl-carbonyl such as methylcarbonyl, ethylcarbonyl, propylcarbonyl, xetc.), (xviii) carbamoyl, (xix) mono-lower alkyl-carbamoyl (e.g. mono-C1-6 alkyl-carbamoyl such as methylcarbamoyl, ethylcarbamoyl, etc.), (xx) di-lower alkyl-carbamoyl (e.g. di-C1-6 alkyl-carbamoyl such as dimethylcarbamoyl, diethylcarbamoyl, etc.), (xxi) lower alkylsulfonyl (e.g. C1-6 alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.), (xxii) lower alkoxy-carbonyl-loweralkyl (e.g. C1-6 alkyl-carbonyl-C1-6 alkyl such as methoxycarbonylmethyl, ethoxycarbonylmethyl, tert-butoxycarbonylmethyt, methoxycarbonylethyl, methoxycarbonylmethyl, methoxycarbbnyl(dimethyl)methyl, ethoxycarbonyl(dimethyl)methyl, tert-butoxycarbonyl(dimethyl)methyl, etc.), (xxiii) carboxy-lower alkyl (e.g. carboxy-C1-6 alkyl such as carboxymethyl, carboxyethyl, carboxy(dimethyl)methyl, etc.), (xxiv) heterocyclic group which may be substituted, (xxv) alkyl which may be substituted, (xxvi) alkoxy which may be substituted, (xxvii) ureido which may be substituted (e.g. ureido, 3-methylureido, 3-ethylureido, 3-phenylureido, 3-(4-fluorophenyl)ureido, 3-(2-methylphenyl)ureido, 3-(4-methoxyphenyl)ureido, 3-(2,4-difluorophenyl)ureido, 3-(3,5-bis(trifluoromethyl)phenyl)ureido, 3-benzylureido, 3-(1-naphtyl)ureido, 3-(2-biphenyl)ureido, etc.), (xxviii) thioureido which may be substituted (e.g. thioureido, 3-methylthioureido, 3-ethylthioureido, 3-phenylthioureido, 3-(4-fluorophenyl)thioureido, 3- (4-methyiphenyl)thioureido, 3-(4-methoxyphenyl)thioureido, 3-(2,4-dichlorophenyl)thioureido, 3-benzylthioureido, 3-(1-naphtyl)thioureido, etc.), (xxix)amidino which may be substituted (e.g. amidino, N1-methylamidino, N1-ethylamidino, N1-phenylamidino, N1,N1-dimethylamidino, N1,N2-dimethylamidino, N1-methyl-,N1-ethylamidino, N1,N1-diethylamidino, N1-methyl-,N1-phenylamidino, N1,N1-di(4-nitrophenyl)amidino, etc.), (xxx) guanidino which may be substituted (e.g. guanidino, 3-mrthylguanidino, 3,3-dimethylguanidino, 3,3-diethylguanidino, etc.), (xxxi) cyclic aminocarbonyl which may be-substituted (e.g. pyrrolidinocarbonyl, piperidinocarpbonyl (4-methylpiperidino)carbonyl, (4-phenylpiperidino)carbonyl, (4-benzylpiperidino)carbonyl, (4-benzoylpiperidino)carbonyl, (4-(4-fluorobenzoyl)piperidino)carbonyl, (4-methylpiperazino)carbonyl, (4-phenylpiperazino)carbonyl, (4-(4-nitrophenyl )piperazino)carbonyl, (4-benzylpiperazino)carbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, etc.), (xxxii) aminothiocarbonyl which may be substituted (e.g. aminothiocarbonyl, methylaminothiocarbonyl, dimethylaminothiocarbonyl, etc.), (xxxiii) aminosulfonyl which may be substituted (e.g. aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, etc.), (xxxiv) phenylsulfonylamino which may be substituted (e.g. phenylsulfonylamino, (4-methylphenyl)sulfonylamino, (4-chlorophenyl)sulfonylamino, (2,5-dichlrophenylsulfonylamino, (4-methoxyphenyl)sulfonylamino, (4-acetylaminophenyl)sulfonylamino, (4-nitrophenyl)phenylsulfonylamino, etc.), (xxxv) sulfo, (xxxvi) sulfino, (xxxvii) sulfeno, (xxxviii) C1-6 alkyl-sulfo (e.g. methylsulfo, ethylsulfo, propylsulfo, etc.), (xxxix) C1-6 alkyl-sulfino (e.g. methylsulfino, ethylsulfino, propylsulfino, etc.), (xxxx) C1-6 alkyl-sulfeno (e.g. methylsulfeno, ethylsulfeno, propylsulfeno, etc.), (xxxxi) phosphono, (xxxxii) di-C1-6 alkoxy-phosphoryl (e.g. dimethoxyphosphoryl, diethoxyphosphoryl, dipropoxyphosphoryl, etc). 1 to 5 (preferably 1 to 3) groups selected from among the above-mentioned groups may be present as substituents.
Preferably, the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d includes but is not limited to: halogen, alkyl which may be substituted, alkoxy which may be substituted, hydroxy, nitro, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, aminothiocarbonyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclic aminocarbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino,5- to 7-membered cycloamino which may have 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino which may be substituted, C1-6 alkylsulfonylamino, amidino which may be substituted, ureido which may be substituted, heterocyclic group which may be substituted.
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d includes those available upon elimination of one hydrogen atom from a monocyclic heteroring, bicyclic heteroring, polycyclic hetero ring such as tricyclic heteroring, tetracyclic heteroring; and so on. The heteroring may be aromatic or nonaromatic. 1 to 6 hetero atoms such as nitrogen, oxygen, sulfur, etc. can be used.
Specifically, the group, available upon elimination of one hydrogen atom from the xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned for ring B. In addition, the group available upon elimination of one hydrogen atom from the monocyclic heteroring such as triazole, thiadiazolel, oxadiazole, oxathiadiazole, triazine, tetrazole, and so on, the bicyclic hetero ring such as indole, dihydroindole, isoindole, dihydroisoindole, benztofuran, dihydrobenzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, indazole, quinoline, tetrahydroquinoline, isoquinoline, tetrahydroisoquinoline, tetrahydro-1H-1-benzazepine, tetrahydro-1H-2-benzazepine, tetrahydro-1H-3-benzazepine, tetrahydrobenzoxazepine, quinazoline, tetrafiydroquinazoline, quinoxaline, tetrahydroquinoxaline, benzodioxan, benzodioxole, benzothiazine imidazopyridine, and so on, polycyclic heteroring (e.g. tricyclic heteroring, tetracyclic heteroring such as acridine, tetrahydroacridine, pyrroloquinoline, pyrroloindole, cyclopentoindole, isoindolobenzazapine, etc.).
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d is preferably the group available upon elimination of one hydrogen atom from the monocyclic or bicyclic heteroring as mentioned above.
The xe2x80x9csubstituentxe2x80x9d for the above xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d includes the groups mentioned for the xe2x80x9csubstituentxe2x80x9d on the xe2x80x9chetero ring which may be substitutedxe2x80x9d for ring B (excluding the above xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d).
As the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9calkyl which may be substitutedxe2x80x9d and the xe2x80x9calkoxy which may be substitutedxe2x80x9d, for example, (i) to (xxiv) and (xxvii) to (xxxxii) of the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chydrocarbon group which may be substituted xe2x80x9d as represented by R1, can be used.
As the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9cureido which may be substitutedxe2x80x9d, xe2x80x9cthioureido which may be substitutedxe2x80x9d, xe2x80x9camidino which may be substitutedxe2x80x9d, xe2x80x9cguanidino which may be substitutedxe2x80x9d, xe2x80x9caminothiocarbonyl which may be substitutedxe2x80x9d, xe2x80x9caminosulfonyl which may be substitutedxe2x80x9d and the xe2x80x9cphenylsulfonylamino which may be substitutedxe2x80x9d, for example, (i) to (xxvi) and (xxxv) to (xxxxii) of the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d as represented by R1, can be used.
The xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d as represented by R1 preferably includes (i) a C1-6 alkyl group, and (ii) a phenyl-C1-6 alkyl group which may be substituted by halogen, nitro, C1-6 alkyl, or C1-6 alkoxy, and more preferably includes benzyl group which may be substituted by C1-4 alkyl (e.g. methyl etc.), trihalogeno-C1-4alkyl (e.g. trihalogeno-methyl etc.), halogen (fluorine, chlorine, etc.), nitro, cyano, C1-4 alkoxy (methoxy etc.), trihalogeno (e.g. fluorine, chlorine, etc.)-C1-4 alkoxy(methoxy etc.), hydroxy, carbamoyl, (4-C1-4 alkyl (e.g. methyl, etc.)-1-piperazinyl)carbonyl, aminothioc-arbonyl, morpholinocarbonyl, carboxyl, C1-4 alkoxy( e.g. methoxy, etc.)-carbonyl, C1-4 alkoxy (e.g. ethoxy, etc.)-carbonyl-C1-4 alkoxy (e.g. methoxy, etc.), carboxyl-C1-4 alkoxy (e.g. methoxy, etc.), C1-4 alkoxy (e.g. ethoxy, etc.)-carbonyl-C1-6alkyl (isopropyl, etc.), carboxyl-C1-6 alyl(isopropyl, etc.), amino, acetylamino, C1-4 alkyl (imethyl, etc.)sulfonylamino, (4-C1-4 alkyl(methyl, etc.)phenyl)sulfonylamino, ureido, 3-C1-4 alkyl(methyl, etc.)-ureido, amidino, dihydrothiazolyl, or dihydroimidazolyl.
More preferably, R1 is a benzyl group which may be substituted by the group consisting of C1-4 alkyl (e.g. methyl etc.), trihalogeno-C1-4 alkyl (e.g. methyl etc.), halogen (fluorine, chlorine, etc.), nitro, cyano, carbamoyl, C1-4 alkoxy( e.g. methoxy, etc.)-carbonyl, C1-4 alkoxy (e.g. ethoxy, etc.)-carbonyl-C1-4 alkoxy (e.g. methoxy, etc.), amino, acetylamino, C1-4 alkyl (methyl, etc.)sulfonylamino, 3-C1-4 alkyl(methyl, etc.)-ureido, amidino, and dihydroimidazolyl.
Still more preferably, R1 is a benzyl group which may be substituted by C1-4 alkyl (e.g. methyl etc.), and furthermore preferably, R1 is a benzyl group which may be substituted by methyl.
The xe2x80x9cacyl groupxe2x80x9d, represented by R11, includes but is not limited to xe2x80x94(Cxe2x95x90O)xe2x80x94R2, xe2x80x94SO2xe2x80x94R2, xe2x80x94SOxe2x80x94R2, xe2x80x94(Cxe2x95x90O)NR3R2, xe2x80x94(Cxe2x95x90O)Oxe2x80x94R2, xe2x80x94(Cxe2x95x90S)Oxe2x80x94R, and xe2x80x94(Cxe2x95x90S)NR3R2 (R2 and R3 may be the same or different and each represents (i) hydrogen atom, (ii) a hydrocarbon group which may be substituted, or (iii) a heterocyclic group which may be substituted, or R2 and R3 may jointly and in combination with the adjacent nitrogen atom form a nitrogen-containing saturated heterocyclic group which may be substituted).
Preferred, among them, are xe2x80x94(Cxe2x95x90O)xe2x80x94R2, xe2x80x94SO2xe2x80x94R2, xe2x80x94SOxe2x80x94R2, xe2x80x94(Cxe2x95x90O)NR3R2, and xe2x80x94(Cxe2x95x90O)Oxe2x80x94R2 (R2 and R3 are as defined above). In particular, xe2x80x94(Cxe2x95x90O)xe2x80x94R2 or xe2x80x94(Cxe2x95x90O)NR3R2 (R2 and R3 are as defined above) is most frequently selected.
The xe2x80x9chydrocarbon groupxe2x80x9d of the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d for R2 and R3 is the group available upon elimination of one hydrogen atom from a hydrocarbon compound. As examples, acyclic or cyclic hydrocarbon groups such as alkyl, alkenyl, alkinyl, cycloalkyl, aryl, and aralkyl groups can be mentioned. Specifically, the same species as those mentioned for the xe2x80x9chydrocarbon groupxe2x80x9d of the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d for R1 can be mentioned. Among them, acyclic or cyclic C1-16 hydrocarbon groups are preferred. Particularly preferred are a lower (C1-6)alkyl group, a lower (C2-6)alkenyl group, a C7-16 aralkyl group, and a C6-14 aryl group. Among them, a lower(C1-6)alkyl group, a C7-16 aralkyl group, and C6-14 aryl are most generally selected.
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d includes the available upon elimination of one hydrogen atom from a monocyclic heteroring, bicyclic heteroring, polycyclic hetero ring such as tricyclic heteroring, tetracyclic heteroring and so on. The heteroring may be aromatic or nonaromatic. 1 to 6 hetero atoms such as nitrogen, oxygen, sulfur, etc. can be used.
Specifically, the group available upon elimination of one hydrogen atom from the xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned for ring B. In addition to, the group available upon elimination of one hydrogen atom from the monocyclic heteroring such as triazole, thiadiazole, oxadiazole, oxathiadiazole, triazine, tetrazole, and so on, the bicyclic hetero ring such as indole, dihydroindole, isoindole, dihydroisoindole, benzofuran, dihydrobenzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, indazole, quinolfine, tetrahydroquinoline, isoquinoline, tetrahydroisoquinoline, tetrahydro-1H-1-benzazepine, tetrahydro-1H-2-benzazepine, tetrahydro-1H-3-benzazepine, tetrahydrobenzoxazepine, quinazoline, tetrahydroquinazoline, quinoxaline, tetrahydroquinoxaline, benzodioxan, benzodioxole, benzothiazine, imidazopyridine, and so on, polycyclic heteroring (e.g. tricyclic heteroring, tetracyclic heteroring such as acridine, tetrahydroacridine, pyrroloquinoline, pyrroloindole, cyclopentoindole, isoindolobenzazapine, etc.).
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d is preferably the group available upon elimination of one hydrogen atom from the monocyclic or bicyclic heteroring as mentioned above.
The xe2x80x9cnitrogen-containing saturated heterocyclic group which may be substitutedxe2x80x9d, which is optionally formed by R2 and R3 in combination with the adjacent nitrogen atom, includes 5- to 9-membered nitrogen-containing heterocyclic groups which may contain 1 to 3 hetero atoms such as nitrogen, oxygen and sulfur in addition to carbon and one nitrogen atom. Preferred among such nitrogen-containing saturated heterocyclic groups is the group having a valence bond on a ring nitrogen atom. The group having a valence bond on a ring nitrogen atom includes groups of the formula 
wherein ring Q1 represents a 5- to 9-membered nitrogen-containing saturated heterocyclic group which may contain 1 or 2 hetero atoms such as nitrogen, oxygen, sulfur, etc., in addition to carbon and one nitrogen atom. For example, the following groups can be generally selected. 
The preferred substituent groups for the xe2x80x9chydrocarbon groupxe2x80x9d and xe2x80x9cheterocyclic groupxe2x80x9d for R2 and R3 and for the xe2x80x9cnitrogen-containing saturated heterocyclic groupxe2x80x9d for NR2R3 include but are not limited to (i) halogen (e.g. fluorine, chlorine, bromine, iodine), (ii) nitro, (iii) cyano, (iv) oxo, (v) hydroxy, (vi) hydrocarbon which may be substituted, (vii) lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, etc.) which may be substituted by phenyl, (viii) lower alkylthio (C1-6 alkylthio such as methylthio, ethylthio, propylthio, etc.) which may be substituted by phenyl, (ix) amino, (x) mono-lower alkylamino (mono-C1-6 alkylamino such as methylamino, ethylamino, propylamino, etc.), (xi) di-lower alkylamino (e.g. di-C1-6 alkylamino such as dimethylamino, diethylamino, etc.), (xii) 5- to 7-membered cycloamino which may have 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur in addition to carbon and one nitrogen atom (e.g. pyrrolidino, piperidino, piperazino, morpholino, thiomorpholino, etc.), (xiii) lower alkyl-carbonylamino (e.g. C1-6 alkyl-carbonylamino such as acetylamino, propionylamino, butyrylamino, etc.), (xiv) lower alkyl-sulfonylamino (e.g. C1-6 alkyl-sulfonylamino such as methylsulfonylamino, thyisulfonylamino etc.), (xv) lower alkoxy-carbonyl (e.g. C1-6 alkoxy-carbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), (xvi) carboxyl, (xvii) lower alkyl-carbonyl (e.g C1-6 alkyl-carbonyl such as methylcarbonyl, ethylcarbonyl, propylcarbonyl, etc.), (xviii) carbamoyl, (xix) mono-lower alkyl-carbamoyl (e.g. mono-C1-6 alkyl-carbamoyl such as methylcarbamoyl, ethylcarbamoyl, etc.), (xx) di-lower alkyl-carbamoyl (e.g. di-C1-6 alkyl-carbamoyl such as dimethylcarbamoyl, diethylcarbamoyl, etc.), (xxi) lower alkylsulfonyl (e.g. C1-6 alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.), (xxii) lower alkoxy-carbonyl-lower alkyl (e.g. C1-6 alkyl-carbonyl-C1-6 alkyl such as methoxycarbonylmethyl, ethoxycarbonylmethyl, tert-butoxycarbonylmethyl, methoxycarbonylethyl, methoxycarbonylmethyl, methoxycarbonyl(dimethyl)methyl, ethoxycarbonyl(dimethyl)methyl, tert-butoxycarbonyl(dimethyl)methyl, etc.), (xxiii) carboxy-lower alkyl (e.g. carboxy-C1-6 alkyl such as carboxymethyl, carboxyethyl, carboxy(dimethyl)methyl, etc.), (xxiv) heterocyclic ring which may be substituted. 1 to 5 (preferably 1 to 3) groups selected from among the above-mentioned groups may be present as substituents.
The above-mentioned xe2x80x9clower alkoxyxe2x80x9d and xe2x80x9clower alkylthioxe2x80x9d may respectively have phenyl as a substituent.
The xe2x80x9chydrocarbonxe2x80x9d and xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chydrocarbon which may be substitutedxe2x80x9d includes the respective groups mentioned for the xe2x80x9chydrocarbon groupxe2x80x9d and xe2x80x9csubstituentxe2x80x9d of the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d which has been mentioned for R1.
The xe2x80x9cheterocyclic ringxe2x80x9d of the xe2x80x9cheterocyclic ring which may be substitutedxe2x80x9d may for example be the group available upon elimination of one hydrogen atom from the xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d represented by ring B.
The xe2x80x9csubstituentxe2x80x9d for the xe2x80x9cheterocyclic ring which (may be substitutedxe2x80x9d includes the same species as mentioned for the substituent for the xe2x80x9chetero ring which may be substitutedxe2x80x9d for ring B (exclusive of the above-mentioned xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d).
The preferred R2 and R3 includes but are not limited to: a phenyl group which may be substituted by C1-4 alkyl (methyl, ethyl, etc.) or C1-4 alkoxy (methoxy, ethoxy, etc.), a C1-4 alkyl group (methyl, ethyl, etc.), a halogeno (e.g. fluoro, chloro, etc.)C1-4 alkyl (methyl, ethyl, etc.) group, a benzyl group, a naphthyl group, a pyridyl group, a thienyl group, a furyl group and hydrogen atom.
The preferred xe2x80x9cacyl groupxe2x80x9d for R1 includes a formyl group, a acetyl group, a trihalogeno (e.g. fluoro, etc.)acetyl group, a pyridylcarbonyl group, a thienylcarbonyl group, a furylcarbonyl group, a phenacyl group, a benzoyl group, a C1-4 alkyl(e.g. methyl, etc.)benzoyl group, C1-4 alkoxy(e.g. methoxy, etc.)benzoyl group, a benzenesulfonyl group, a naphthylsulfonyl group, and a thienylsulfonyl group. And more preferably, xe2x80x94(Cxe2x95x90O)xe2x80x94R2xe2x80x2 (where R2xe2x80x2 represents a phenyl or phenyl-C1-6 alkyl group, which may be substituted by C1-6 alkyl or C1-6 alkoxy).
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d for R1 may be the group available upon elimination of one hydrogen atom from a monocyclic heteroring, bicyclic heteroring, polycyclic hetero ring such as tricyclic heteroring, tetracyclic heteroring and so on. The heteroring may be aromatic or nonaromatic. 1 to 6 hetero atoms such as nitrogen, oxygen, sulfur, etc. can be used.
Specifically, the group available upon elimination of one hydrogen atom from the xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned for ring B. In addition to, the group available upon elimination of one hydrogen atom from the monocyclic heteroring such as triazole, thiadiazole, oxadiazole, oxathiadiazole, triazine, tetrazole, and so on, the bicyclic hetero ring such as indole, dihydroindole, isoindole, dihydroisoindole, benzofuran, dihydrobenzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, indazole, quinoline, tetrahydroquinoline, isoquinoline, tetrahydroisoquinoline, tetrahydro-1H-1-benzazepine, tetrahydro-1H-2-benzazepine, tetrahydro-1H-3-benzazepine, tetrahydrobenzoxazepine, quinazoline, tetrahydroquinazoline, quinoxaline, tetrahydroquinoxaline, benzodioxan, benzodioxole, benzothiazine, imidazopyridine, and so on, polycyclic heteroring (e.g. tricyclic heteroring, tetracyclic heteroring such as acridine, tetrahydroacridine, pyrroloquinoline, pyrroloindole, cyclopentoindole, isoindolobenzazapine, etc.).
The xe2x80x9cheterocyclic groupxe2x80x9d of the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d is preferably the group available upon elimination of one hydrogen atom from the monocyclic or bicyclic heteroring as mentioned above, and is morepreferably, a pyridyl group can be uded.
The xe2x80x9csubstituentxe2x80x9d for the above xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d includes the groups mentioned for the xe2x80x9csubstituentxe2x80x9d on the xe2x80x9chetero ring which may be substitutedxe2x80x9d for ring B (excluding the above xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d), and the xe2x80x9csubstitutionxe2x80x9d for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d which has been mentioned for R1.
Preferably, R1 represents (i) a hydrogen atom, (ii) a C1-6 alkyl group, (iii) a phenyl-C1-6 alkyl group which may be substituted by halogen, nitro, C1-6 alkyl or C1-6 alkoxy, or (iv) xe2x80x94(Cxe2x95x90O)xe2x80x94R2xe2x80x2 (where R2xe2x80x2 represents a phenyl or phenyl-C1-6 alkyl group, which may be substituted by C1-6 alkyl or C1-6 alkoxy).
The group which is formed as the xe2x80x9cphenylxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a monocyclic hetero ring which may be substituted specifically includes groups of the following formula 
which are available upon elimination of one hydrogen atom each from bicyclic benzenoid systems such as 2,3-dihydrobenzofuran; 3,4-dihydro-2H-1-benzothiopyran; 2,3-dihydro-1H-indole; 1,2,3,4-tetrahydroquinoline; 2,3-dihydro-1H-isoindole; 1,2,3,4-tetrahydroisoquinoline; benzazepines such as 2,3,4,5-tetrahydro-1H-1-benzazepine, 2,3,4,5-tetrahydro-1H-2-benzazepine, 2,3,4,5-tetrahydro-1H-3-benzazepine, etc.; benzazocines such as 1,2,3,4,5,6-hexahydro-1-benzazocine, 1,2,3,4,5,6-hexahydro-2-benzazocine, 1,2,3,4,5,6-hexahydro-3-benzazocine, etc.; benzazonines such as 2,3,4,5,6,7-hexahydro-1H-1-benzazonine, 2,3,4,5,6,7-hexahydro-1H-2-benzazonine, 2,3,4,5,6,7-hexahydro-1H-3-benzazonine, 2,3,4,5,6,7-hexahydro-1H-4-benzazonine, etc.; benzoxazoles such as 2,3-dihydrobenzoxazole etc.; benzothiozoles such as 2,3-dihydrobenzothiazole etc.; benzimidazoles such as 2,3-dihydro-1H-benzimidazole, etc.; benzoxazines such as 3,4-dihydro-1H-2,1-benzoxazine, 3,4-dihydro-1H-2,3-benzoxazine, 3,4-dihydro-2H-1,2-benzoxazine, 3,4-dihydro-2H-1,4-benzoxazine, 3,4-dihydro-2H-1,3-benzoxazine, 3,4-dihydro-2H-3,1-benzoxazine, etc.; benzothiazines such as 3,4-dihydro-1H-2,1-benzothiazine, 3,4-dihydro-1H-2,3-benzothiazine, 3,4-dihydro-2H-1,2-benzothiazine, 3,4-dihydro-2H-1,4-benzothiazine, 3,4-dihydro-2H-1,3-benzothiazine, 3,4-dihydro-2H-3,1-benzothiazine; etc.; benzodiazines such as 1,2,3,4-tetrahydrocinnoline, 1,2,3,4-tetriahydrophthalazine, 1,2,3,4-tetrahydroquinazoline, 1,2,3,4-tetrahydroquinoxaline, etc.; benzoxathiins such as 3,4-dihydro-1,2-benzoxathiin, 3,4-dihydro-2,1-benzoxathiin, 2,3-dihydro-1,4-benzoxathiin, 1,4-dihydro-2,3-benzoxathiin, 4H-1,3-benzoxathiin, 4H-3,1-benzoxathiin, etc.; benzodioxins such as 3,4-dihydro-1,2-benzodioxin, 2,3-dihydro-1,4-benzodioxin, 1,4-dihydro-2,3-benzodioxin, 4H-1,3-benzodioxin, etc.; benzodithiins such as 3,4-dihydro-1,2-benzodithiin, 2,3-dihydro-1,4-benzodithiin, 1,4-dihydro-2,3-benzodithiin, 4H-1,3-benzodithiin, etc.; benzoxazepines such as 2,3,4,5-tetrahydro-1,2-benzoxazepine, 2,3,4,5-tetrahydro-1,3-benzoxazepine, 2,3,4,5-tetrahydro-1,4-benzoxazepine, 2,3,4,5-tetrahydro-1,5-benzoxazepine, 1,3,4,5-tetrahydro-2,1-benzoxazepine, 1,3,4,5-tetrahydro-2,3-benzoxazepine, 1,3,4,5-tetrahydro-2,4-benzoxazepine, 1,2,4,5-tetrahydro-3,1-benzoxazepine, 1,2,4,5-tetrahydro-3,2-benzoxazepine, 1,2,3,5-tetrahydro-4,1-benzoxazepine, etc.; benzothiazepines such as 2,3,4,5-tetrahydro-1,2-benzothiazepine, 2,3,4,5-tetrahydro-1,4-benzothiazepine, 2,3,4,5-tetrahydro-1,5-benzothiazepine, 1,3,4,5-tetrahydro-2,1-benzothiazepine, 1,3,4,5-tetrahydro-2,4-benzothiazepine, 1,2,4,5-tetrahydro-3,1-benzothiazepine, 1,2,4,5-tetrahydro-3,2-benzothiazepine, 1,2,3,5-tetrahydro-4,1-benzothiazepine, etc.; benzodiazepines such as 2,3,4,5-tetrahydro-1H-1,2-benzodiazepine, 2,3,4,5-tetrahydro-1H-1,3-benzodiazepine, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine, 2,3,4,5-tetrahydro-1H-2,3-benzodiazepine, 2,3,4,5-tetrahydro-1H-2,4-benzodiazepine, etc.; benzodioxepins such as 4,5-dihydro-1,3-benzodioxepin, 4,5-dihydro-3H-1,2-benzodioxepin, 2,3-dihydro-5H-1,4-benzodioxepin, 3,4-dihydro-2H-1,5-benzodioxepin, 4,5-dihydro-1H-2,3-benzodioxepin, 1,5-dihydro-2,4-benzodioxepin, etc.; benzodithiepins such as 4,5-dihydro-1H-2,3-benzodithiepin, 1,5-dihydro-2,4-benzodithiepin, 3,4-dihydro-2H-1,5-benzodithiepin, 2,3-dihydro-5H-1,4-benzodithiepin, etc.; benzoxazocinesgsuch as, 3,4,5,6-tetrahydro-2H-1,5-benzoxazocine, 3,4,5,6-tetrahydro-2H-1,6-benzoxazocine, etc.; benzothiazocines such as 3,4,5,6-tetrahydro-2H-1,5-benzothiazocine, 3,4,5,6-tetrahydro-2H-1,6-benzothiazocine, etc.; benzodiazocines such as 1,2,3,4,5,6-hexahydro-1,6-benzodiazocine etc.; benzoxathiocines such as 2,3,4,5-tetrahydro-1,6-benzoxathiocine etc.; benzodioxocines such as 2,3,4,5-tetrahydro-1,6-benzodioxocine etc.; benzotrioxepins such as 1,3,5-benzotrioxepin, 5H-1,3,4-benzotrioxepin, etc.; benzoxathiazepines such as 3,4-dihydro-1H-5,2,1-benzoxathiazepine, 3,4-dihydro-2H-5,1,2-benzoxathiazepine, 4,5-dihydro-3,1,4-benzoxathiazepine, 4,5-dihydro-3H-1,2,5-benzoxathiazepine, etc.; benzoxadiazepines such as 2,3,4,5-tetrahydro-1,3,4-benzoxadiazepine etc.; benzothiadiazepines such as 2,3,4,5-tetrahydro-1,3,5-benzothiadiazepine etc.; benzotriazepines such as 2,3,4,5-tetrahydro-1H-1,2,5-benzotriazepine etc.; benztxathiepins such as 4,5-dihydro-1,3,2-benzoxathiepin, 4,5-dihydro-1H-2,3-benzoxathiepin, 3,4-dihydro-2H-1,5-benzoxathiepin, 4,5-dihydro-3H-1,2-benzoxathiepin, 4,5-dihydro-3H-2,1-benzoxathiepin, 2,3-dihydro-5H-1,4-benzoxathiepin, 2,3-dihydro-5H-4,1-benzoxathiepin, etc. Particularly preferred are groups available upon elimination of one hydrogen atom each from such bicyclic benzenoid systems as 2,3,4,5-tetrahydro-1H-3-benzazepine, 2,3,4,5-tetrahydro-1H-2-benzazepine, 2,3-dihydro-1H-indolet 2,3,4,5-tetrahydro-1,4-benzoxazepine, and so forth.
As preferred examples of the group formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a monocyclic hetero ring which may be substituted, groups of the following formula can be mentioned. 
wherein ring B represents a 5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxo in addition to R1; ring A and R1 are as defined herein before.
The xe2x80x9c5- to 9-membered nitrogen-containing hetero ringxe2x80x9d of the xe2x80x9c5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxoxe2x80x9d includes 5- to 9-membered nitrogen-containing hetero rings which may contain 1 to 3 hetero atoms, e.g. nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom. Preferably, 5- to 9-membered nonaromatic nitrogen-containing hetero rings (such as pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, etc.) are selected. The following are particularly preferred examples of the group formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenylgroup which may be substituted and/or condensedxe2x80x9d is fused to a monocyclic hetero ring: 
wherein R1 is as defined herein before, for the best result, the groups represented as following formula: 
wherein R1 is as defined herein before, can be used.
The group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a bicyclic hetero system which may be substituted or two similar or dissimilar rings at least one of which isand monocyclic hetero ring, which may be substituted, includes but is not limited to groups of the following formula. 
wherein ring A is as defined hereinbefore; ring C and ring D are such that one represents a hetero ring which may be substituted with the other being a 5- to 9-membered ring which may be substituted and optionally containing one or more hetero atoms.
The xe2x80x9chetero ringxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned above for either ring C or ring D includes but is not limited to 4- to 14-membered hetero rings, preferably 5- to 9-membered hetero rings, each containing 1 to 3 hetero atoms such as nitrogen, oxygen and/or sulfur as ring members. This hetero ring may be whichever of an aromatic hetero ring and a nonaromatic hetero ring. Thus, for example, pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperaziner, tetrahydrooxazepine, morpholine, thiomorpholine, etc. can be mentioned.
The xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chetero ring which may be substitutedxe2x80x9d has the same meaning as the xe2x80x9csubstituentxe2x80x9d for the xe2x80x9chetero ring which may be substitutedxe2x80x9d which has been mentioned for ring B.
The xe2x80x9c5- to 9-membered ring optionally containing one or more hetero atomsxe2x80x9d of the xe2x80x9c5- to 9-membered ring which may be substituted and optionally containing one or more hetero atomsxe2x80x9d which has been mentioned for either ring C or ring D includes 5- to 9-membered hetero rings (e.g. pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, etc.) and 5- to 9-membered carbocyclic rings.
The xe2x80x9c5- to 9-membered carbocyclic ringxe2x80x9d mentioned above may be a saturated ring or an unsaturated ring and is preferably selected from among benzene, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene, cycloheptane, cycloheptene, cycloheptadiene, and so forth. Particularly, benzene or cyclohexane is preferred.
The xe2x80x9csubstituentxe2x80x9d for the xe2x80x9c5- to 9-membered ring which may be substituted and optionally containing one or more hetero atomsxe2x80x9d has the same meaning as the xe2x80x9csubstituent for any carbon atomxe2x80x9d of the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned for ring B.
The group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a bicyclic hetero system which may be substituted includes:
(1) the phenyl group fused to a bicyclic hetero system corresponding to the group available upon elimination of one hydrogen atom from the benzene ring of a tricyclic benzenoid system of the formula 
xe2x80x83e.g. carbazole, 1,2,3,4,4a,9a-hexahydrocarbazole, 9,10-dihydroacridine, 1,2,3,4-tetrahydroacridine, 10,11-dihydro-5H-dibenz[b,f]azepine, 5,6,7,12-tetrahydrodibenz[b,g]azocine, 6,11-dihydro-5H-dibenz[b,e]azepine, 6,7-dihydro-5H-dibenz[c,e]azepine, 5,6,11,12-tetrahydrodibenz[b,f]azocine, dibenzofuran, 9H-xanthene, 10,11-dihydrodibenz[b,f]oxepin, 6,11-dihydrodibenz[b,e]oxepin, 6,7-dihydro-5H-dibenz[b,g]oxocine, dibenzothiophene, 9H-thioxanthene, 10,11-dihydrodibenzo[b,f]thiepin, 6,11-dihydrodibenzo[b,e]thiepin, 6,7-dihydro-5H-dibenzo[b,g]thiocine, 10H-phenothiazine, 10H-phenoxazine, 5,10-dihydrophenazine, 10,11-dibenzo[b,f][1,4]thiazepine, 10,11-dihydrodibenz[b,f][1,4]oxazepine, 2,3,5,6,11,11a-hexahydro-1H-pyrrolo[2,1-b][3]benzazepine, 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepine, 5,11-dihydrodibenz[b,e][1,4]oxazepine, 5,11-dihydrodibenzo[b,f][1,4]thiazepine, 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepine, 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole, etc.;
(2) the bicyclic hetero system-fused phenyl group of the formula 
xe2x80x83which corresponds to the group available upon elimination of one hydrogen atom from the benzene ring of a tricyclic benzenoid system and, as such, includes but is not limited to 1H,3H-naphth[1,8-cd][1.2]oxazine, naphth[1,8-de]-1,3-oxazine, naphth[1,8-de]-1,2-oxazine, 1,2,2a,3,4,5-hexahydrobenz[cd]indole, 2,3,3a,4,5,6-hexahydro-1H-benzo[de]quinoline, 4H-pyrrolo[3,2,1-ij]quinoline, 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinoline, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline, 1H,5H-benzo[ij]quinoliizine, azepino[3,2,1-hi]indole, 1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole, 1H-pyrido[3,2,1-jk][1]benzazepine, 5,6,7,8-tetrahydro-1H-pyrido[3,2,1-jk][1]benzazepine, 1,2,5,6,7,8-hexahydro-1H-pyrido[3,2,1-jk][1]benzazepine, 2,3-dihydro-1H-benz[de]isoquinolinet 1,2,3,4,4a,5,6,7-octahydronaphth[1,8-bc]azepine, 2,3,5,6,7,8-hexahydro-1H-pyrido[3,2,1-jk][1]benzazepine, etc.;
(3) thephenyl group fused to two similar or dissimilar rings (at least one of the two rings is a monocyclic hetero ring), which corresponds to the group tricyclic benzenoid system of the formula 
xe2x80x83and, as such, includes but is no limited to 1,2,3,5,6,7-hexahydrobenzo[1,2-b:4,5-b,]dipyrrole, 1,2,3,5,6,7-hexahydrocyclopent[f]indole, etc.; and
(4) the phenyl group fused to two similar or dissimilar rings (at least one of the two rings is a monocyclic hetero ring), which corresponds to the group available upon elimination of one hydrogen atom from a tricyclic benzenoid system of the formula 
xe2x80x83and, as such, includes but is not limited to 1,2,3,6,7,8-hexahydrocyclopent[e]indole, 2,3,4,7,8,9-hexahydro-1H-cyclopenta[f]quinoline, and so forth.
The preferred group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a bicyclic hetero system includes groups of the formula 
wherein ring Cxe2x80x2 and ring Dxe2x80x2 independently represent a 5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxo in addition to R1; ring A, ring D, and R1 are as defined hereinbefore.
The xe2x80x9c5- to 9-membered nitrogen-containing hetero ringxe2x80x9d, of the xe2x80x9c5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxoxe2x80x9d includes 5- to 9-membered nitrogen-containing hetero rings which may contain 1 to 3 hetero atoms, such as nitrogen, oxygen, and/or sulfur, in addition to carbon and one nitrogen atom. Preferred are 5- to 9-membered nonaromatic nitrogen-containing hetero rings (e.g. pyrrolidine, piperidine, hexamethylenedimine, heptamethyleneimine, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, etc.).
The still more preferred group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl grop which may be substituted and/or condensedxe2x80x9d is fused to a bicyclic hetero system includes groups of the following formula: 
wherein R1 is as defined hereinbefore.
The group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a tricyclic hetero system which may be substituted includes but is not limited to groups of the following formula: 
wherein ring A is as defined hereinbefore; ring E, ring F, and ring G are such that at least one of the three rings is a hetero ring which may be substituted, with the other ring or rings each representing a 5- to 9-membered ring which may be substituted and optionally containing one or more hetero atoms.
The xe2x80x9chetero ringxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the xe2x80x9chetero ring which may be substitutedxe2x80x9d as mentioned for at least one of ring E, ring F, and ring G includes the rings and substituent groups specifically mentioned for the xe2x80x9chetero ringxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the xe2x80x9chetero ring which may be substitutedxe2x80x9d for rings C and D.
The xe2x80x9c5- to 9-membered ring optionally containing one or more hetero atomsxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the xe2x80x9c5- to 9-membered hetero ring which may be substituted and optionally containing one or more hetero atomsxe2x80x9dwhich has been mentioned for ring E, ring F, and/or ring G includes the rings and groups specifically mentioned for the xe2x80x9c5- to 9-membered ring optionally containing one or more hetero atomsxe2x80x9d of, and xe2x80x9csubstituentsxe2x80x9d on, the xe2x80x9c5- to 9-membered hetero ring which may be substituted and optionally containing one or more hetero atomsxe2x80x9d which has been mentioned for ring C or ring D.
The group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a tricyclic hetero system which may be substituted more specifically includes (1) the phenyl group fused to a tricyclic hetero system: 
where ring Exe2x80x2 and ring Fxe2x80x2 are defined hereinafter, which corresponds to the group available upon elimination of one hydrogen atom from the benzene ring of a tetracyclic hetero system and, as such, includes but is not limited to 2H-isoindolo[2,1-e]purine, 1H-pyrayzolo[4xe2x80x2,3xe2x80x2:3,4]pyrido[2,1-a]isoindole, 1H-pyrido[2xe2x80x2,3xe2x80x2:4,5]imidazo[2,1-a]isoindole, 2H,6H-pyrido[1xe2x80x2,2xe2x80x2:3,4]imidazo[5,1-a]isoindole, 1H-isoindolo[2,1-a]benzimidazole, 1H-pyrido[3xe2x80x2,4xe2x80x2:4,5]pyrrolo[2,1-a]isoindole, 2H-pyrido[4xe2x80x2,3xe2x80x2:4,5]pyrrolo[2,1-a]isoindole, 1H-isoindolo[2,1-a]indole, 2H-isoindolo[1,2-a]isoindole, 1H-cyclopenta[4,5]pyrimido[2,1-a]isoindole, 2H,4H-pyrano[4xe2x80x2,3xe2x80x2:4,5][1,3]oxazino[2,3-a]isoindole, 2H-isoindolo[2;1-a][3,1]benzoxazine, 7H-isoindolo[1,2-b][1,3]benzoxazine, 2H-pyrido[2xe2x80x2,1xe2x80x2:3,4]pyrazino[2,1-a]isoindole, pyrido[2xe2x80x2,3xe2x80x2:4,5]pyrimido[2,1-a]isoindole, pyrido[3xe2x80x2,2xe2x80x2:5,6]pyrimido[2,1-a]isoindole, 1H-pyrido[1,2xe2x80x2:3,4]pyrimido[2,1-a]isoindole, isoindolo[2,1-a]quinazoline, isoindolo[2,1-a]quinoxaline, isoindolo[1,2-a]isoquinoline, isoindolo[2,1-b]isoquinoline, isoindolo[2,1-a]quinoline, 6H-oxazino[3xe2x80x2,4xe2x80x2:3,4][1,4]diazepino[2,1a]isoindole, azepino[2xe2x80x2,1xe2x80x2:3,4]pyrazino[2,1-a]isoindole, 2H,6H-pyrido[2xe2x80x2,1xe2x80x2:3,4][1,4]diazepino[2,1-a]isoindole, 1H-isoindolo[1,2-b][1,3,4]benzotriazepine, 2H-isoindolo[2,1-a][1;3,4]benzotriazepine, isoindolo[2,1-d][1,4]benzoxazepine, 1H-isoindolo[2,1-b][2,4]benzodiazepine, 1H-isoindolo[2,1-c][2,3]benzodiazepine, 2H-isoindolo[1,2-a][2,4]benzodiazepine, 2H-isoindolo[2,1-d][1,4]benzodiazepine, 5H-indolo[2,1-b][3]benzazepine, 2H-isoindolo[1,2-a][2]benzazepine, 2H-isoindolo[1,2-b][3]benzazepine, 2H-isoindolo[2,1-b][2]benzazepine, 2H-isoindolo[1,2-b][1,3,4]benzoxadiazocine, isoindolo[2,1-b][1,2,6]benzotriazocine, 5H-4,8-methano-1H-[1,5]diazacycloundecino[1,11-a]indole, etc.;
(2) the phenyl group fused to a tricyclic hetero system: 
xe2x80x83wherein ----- represents a single bond or a double bond; ring Exe2x80x2 and ring Gxe2x80x2 are as defined hereinafter, which corresponds to the group available upon elimination of one hydrogen atom from a tetracyclic benzenoid system and, as such, includes 1H,4H-pyrrolo[3xe2x80x2,2xe2x80x2:4,5]pyrrolo[3,2,1-ij]quinoline, pyrrolo[3,2,1-jk]carbazole, 1H-furo[2xe2x80x2,3xe2x80x2:4,5]pyrrolo[3,2,1-ij]quinoline, 1H,4H-cyclopenta[4,5]pyrrolo[1,2,3-de]quinoxaline, 1H,4H-cyclopenta[4,5]pyrrolo[312,1-ij]quinoline, pyrido[3xe2x80x2,4xe2x80x2:4,5:]pyrrolo[1,2,3-de]benzoxazine, [1,4]oxazino[2,3,4-jk]carbazole; 1H,3H-[1,3]oxazino[5,4,3-jk]carbazole, pyrido[3xe2x80x2,4xe2x80x2:4,5]pyrrolo[1,2,3-de][1,4]benzothiazine, 4H-pyrrolo[3,2,1-de]phenanthridine, 4H,5H-pyrido[3,2,1-de]phenanthridine, 1H,4H-3a,6a-diazafluoranthene, 1-oxa-4,6a-diazafluoranthene, 4-oxa-2,10b-diazafluoranthene, 1-thia-4,6a-diazafluoranthene, 1H-pyrazino[3,2,1-jk]carbazole, 1H-indolo[3,2,1-de][1,5]naphthyridine, benzo[b]pyrano[2,3,4-hi]indolizine, 1H,3H-benzo[b]pyrano[3,4,5-hi]indolizine, 1H,4H-pyrano[2xe2x80x2,3xe2x80x2:4,5]pyrrolo[3,2,1-ij]quinoline, 1H,3H-benzo[b]thiopyrano[3,4,5-hi]indolizine, 1H-pyrido[3,2,1-jk]carbazole, 4H-3-oxa-11b-azacyclohepta[jk]fluorene, 2H-azepino[1xe2x80x2,2xe2x80x2:1,2]pyrimidino[4,5-b]indole, 1H,4H-cyclohepta[4,5]pyrrolo6[1,2,3-de]quinoxaline, 5H-pyrido[3xe2x80x2,4xe2x80x2:4 5]pyrrolo[1,2,3-ef][1,5]benzoxazepine, 4H-pyrido[3xe2x80x2,4xe2x80x2:4,5]pyrrolo[3,2,1-jk][4,1]benzothiazepine, 5H-pyrido[3xe2x80x2,4xe2x80x2:4,5]pyrrolo[1,2,3-ef][1,5]benzothiazepine, 5H-pyrido[4xe2x80x21,3xe2x80x2:4,5]pyrrolo[1,2,3-ef][1,5]benzothiazepine, [1,2,4]triazepino[6,5,4-jk]carbazole, [1,2,4]triazepino[6,7,1-jk]carbazole, [1,2,5]triazepino[3,4,5-jk]carbazole, 5H-[1,4]oxazepino[2,3,4-jk]carbazole, 5H-[1,4]thiazepino[2,3,4-jk]carbazole, [1,4]diazepino[3,2,1-jk]carbazole, [1,4]diazepino[6,7,1-jk]carbazole, azepino[3,2,1-jk]carbazole 1H-cycloocta[4,5]pyrrolo[1,2,3-de]quinoxaline, and 1H-cycloocta[4,5]pyrrolo[3,2,1-ij]quinoline;
(3) the phenyl group fused to a tricyclic hetero ring: 
xe2x80x83where ----- represents a single bond or a double bond; ring Exe2x80x2 and ring Fxe2x80x2 are as defined hereinafter, which; corresponds to the group available upon elimination of one hydrogen atom from a tetracyclic benzenoid system and, as such, includes but is not limited to 1H-indolo[1,2-a]benzimidazole, 1H-indolo[1,2-b]indazole, pyrrolo[2xe2x80x2,1xe2x80x2:3,4]pyrazino[1,2-a]indole, 1H,5H-pyrrolo[1xe2x80x2,2xe2x80x2:4,5]pyrazino[1,2-a]indole 2H-pyrido[2xe2x80x2,3xe2x80x2:3,4]pyrrolo[1,2-a]indole, 1H-pyrrolo[2xe2x80x2,3xe2x80x2:3,4]pyrido[1,2-a]indole, 1H-indolo[1,2-a]indole, 6H-isoindolo[2,1-a]indole, 6H-indolo[1,2-c][1,3]benzoxazine, 1H-indolo[1,2-b][1,2]benzothiazine, pyrimido[4xe2x80x2,5xe2x80x2:4,5]pyrimido[1,6-a]indole, pyrazino[2xe2x80x2,3xe2x80x2:3,4]pyrido[1,2-a]indole, 6H-pyrido[1xe2x80x2,2xe2x80x2:3,4]pyrimido[1,6-a]indole, indolo[1,2-b]cinnoline, indolo[1,2-a]quinazoline, indolo[1,2-c]quinazoline, indolo[2,1-b]quinazoline, indolo[1,2-a]quinoxaline, indolo[1,2-a][1,8]naphthyridine, indolo[1,2-b]-2,6-naphthyridine, indolo[1,2-b][2:,7]naphthyridine, indolo[1,2-h]-1,7-naphthyridine, indolo[1,2-b]isoquinoline, indolo[2,1-a]isoquinoline, indolo[1,2-a]quinoline, 2H,6H-pyrido[2xe2x80x2,1xe2x80x2:3,4][1,4]diazepino[1,2-a]indole, 1H-indolo[2,1-c][1,4]benzodiazepine, 2H-indolo[1,2-d][1,4]benzodiazepine, 2H-indolo[1,2-a][2,3]benzodiazepine, 2H-indolo[2,1-b][1,3]benzodiazepine, 1H-indolo[1,2-b][2]benzazepine, 2H-indolo[1,2-a][1]benzazepine, 2H-indolo[2,1-a][2]benzazepine, indolo[1,2-e][1,5]benzodiazocine, and indolo[2,1-b][3]benzazocine;
(4) the phenyl group fused to a tricyclic heterocyclic ring: 
xe2x80x83wherein ----- represents a single bond or a double bond; ring Exe2x80x2 is as defined hereinafter, which corresponds to the group available upon elimination of one hydrogen atom from a tetracyclic benzenoid system and, as such, includes but is not limited to 1H-imidazo[1xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, 1H-imidazo[1xe2x80x2,2xe2x80x2:1,6]pyrido[4,3-b]indole, 1H-imidazo[1xe2x80x2,5xe2x80x2:1,2]pyrido[3,4-b]indole, 1H-imidazo[1xe2x80x2,5xe2x80x2:1,6]pyrido[4,3-b]indole, 1H-pyrido[2xe2x80x2,1xe2x80x2:2,3]imidazo[4,5-b]indole, imidazo[4,5-a]carbazole, imidazo[4,5-c]carbazole, pyrazolo[3,4-c]carbazole, 2H-pyrazino[1xe2x80x2,2xe2x80x2:1,5]pyrrolo[2,3-b]indole, 1H-pyrrolo[1,xe2x80x2,2xe2x80x2:1,2]pyrimido[4,5-b]indole, 1H-indolizino[6,7-b]indole, 1H-indolizino[8,7-b]indole, indolo[2,3-b]indole; indolo[3,2-b]indole, pyrrolo[2,3-a]carbazole, pyrrolo[2,3-b]carbazole, pyrrolo[2,3-c]carbazole, pyrrolo[3,2-a]carbazole, pyrrolo[3,2-b]carbazole, pyrrolo[3,2-c]carbazole, pyrrolo[3,4-a]carbazole, pyrrolo[3,4-b]carbazole, pyrrolo[3,4-c]carbazole, 1H-pyrido[3xe2x80x2,4xe2x80x2:4,5]furo[3,2-b]indole, 1H-furo[3,4-a]carbazole, 1H-furo[3,4-b]carbazole, 1H-furo[3,4-c]carbazole, 2H-furo[2,3-a]carbazole, 2H-furo[2,3-c]carbazole, 2H-furo[3,2-a]carbazole, 2H-furo[3,2-c]carbazole, 1H-pyrido][3xe2x80x2,4xe2x80x2:4,5]thieno[2,3-b]indole, thieno[3xe2x80x2,2xe2x80x2:5,6]thiopyrano[4,3-b]indole, thieno[3xe2x80x2,4xe2x80x2:5,6]thiopyrano[4,3-b]indole, 1H-[1]benzothieno[2,3-b]indole, 1H-[1]benzothieno[3,2-b]indole, 1H-thieno[3,4-a]carbazole, 2H-thieno[2,3-b]carbazole, 2H-thieno[3,2-a]carbazole, 2H-thieno[3,2-b]carbazole, cyclopenta[4,5]pyrrolo[2,3-f]quinoxaline, cyclopenta[5,6]pyrido[2,3-b]indole, pyrido[2xe2x80x2,3xe2x80x2:3,4]cyclopenta[1,2-b]indole, pyrido[2xe2x80x2,3xe2x80x2:4,5]cyclopenta[1,2-b]indole, pyrido[3xe2x80x2,4xe2x80x2:3,4]cyclopenta[1,2-b]indole, pyrido[3xe2x80x2,4xe2x80x2:4,5]cyclopenta[1,2-b]indole, pyrido[4xe2x80x2,3xe2x80x2:4,5]cyclopenta[1,2-b]indole, 1H-cyclopenta[5,6]pyrano[2,3-b]indole, 1H-cyclopenta[5,6]thiopyrano[4,3-b]indole, cyclopenta[a]carbazole, cyclopenta[c]carbazole, indeno[1,2-b]indole, indeno[2,1-b]indole, [1,2,4]triazino[4xe2x80x2,3xe2x80x2:1,2]pyrido[3,4-b]indole, 1,3,5-triazino[1xe2x80x2,2xe2x80x2:1,1]pyrido[3,4-b]indole, 1H-[1,4]oxazino[4xe2x80x2,3xe2x80x2:1,2]pyrido[3,4-b]indole, 1H-[1,4]oxazino[4xe2x80x2,3xe2x80x2:1,6]pyrido[3,4-b]indole, 4H-[1,3]oxazino[3xe2x80x2,4xe2x80x2:1,2]pyrido[3,4-b]indole, indolo[3,2-b][1,4]benzoxazine, 1,3-oxazino[6,5-b]carbazole, 2H-pyrimido[2xe2x80x2,1xe2x80x2:2,3][1,3]thiazino[5,6-b]indole, 2H-[1,3]thiazino[3xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, 4H-1,3]thiazino[3xe2x80x2,4xe2x80x2:1,2]pyrido[3,4-b]indole, indolo[2,3-b][1,4]benzothiazine, indolo[3,2-b[1,4]benzothiazine, indolo[3,2-c][2,1]benzothiazine, 1,4-thiazino[2,3-a]carbazole, [1l,4]thiazino[2,3-b]carbazole, [1,4]thiazino[2,3-c]carbazole, 1,4-thiazino[3,2-b]carbazole, 1,4-thiazino[3,2-c]carbazole, 1H-indolo[2,3-g]pteridine, 1H-indolo[3,2-g]pteridine, pyrazino[1xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, pyrazino[1xe2x80x2,2xe2x80x2:1,2]pyrido[4,3-b]indole, 1H-pyrido[2xe2x80x2,3xe2x80x2:5,6]pyrazino[2,3-b]indole, 1H-pyrido[3xe2x80x2,2xe2x80x2:5,6]pyrazino[2,3-b]indole, 1H-pyrido[3xe2x80x2,4xe2x80x2:5,6]pyrazino[2,3-b]indole, pyrido[1xe2x80x2,2xe2x80x2:1,2]pyrimido[4,5-b]indole, pyrido[1xe2x80x2,2xe2x80x2:1,2]pyrimido[5,4-b]indole, pyrido[2xe2x80x2,1xe2x80x2:2,3]pyrimido[4,5-b]indole, pyrimido[1xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, pyrimido[1xe2x80x2,2xe2x80x2:1,6]pyrido[3,4-b]indole, pyrimido[5xe2x80x2,4xe2x80x2:5,6]pyrano[2,3-b]indole, pyridazino[4xe2x80x2,5xe2x80x2:5,6]thiopyrano4,5-b]indole, 1H-indolo[3,2-c]cinnoline, 1H-indolo[2,3-b]quinoxaline, 1H-pyrazino[2,3-a]carbazole, 1H-pyrazino[2,3-b]carbazole, 1H-pyrazino[2,3-c]carbazole, 1H-pyridazino[3,4-c]carbazole, 1H-pyridazino[4,5-b]carbazole, 1H-pyrimido[4,5-a]carbazole, 1H-pyrimido[4,5-c]carbazole, 1H-pyrimido[5,4-a]carbazole, 1H-pyrimido[5,4-b]carbazole, 1H-pyrimido[5,4-c]carbazole, 7H-1,4-dioxino[2xe2x80x2,3xe2x80x2:5,6][1,2]dioxino[3,4-b]indole, 6H-[1,4]benzodioxino[2,3-b]indole, 6H-[1,4]benzodioxino[2,3-b]indole, 1H-indolo[2,3-b]-1,5-naphthyridine, 1H-indolo[2,3-b][1,6]naphthyridine, 1H-indolo[2,3-b][1,8]naphthyridine, 1H-indolo[2,3-c]-1,5-naphthyridine, 1H-indolo[2,3-c][1,6]naphthyridine 1H-indolo[2,3-c][1,7]naphthyridine, 1H-indolo[2,3-c][1,8]naphthyridine, 1H-indolo[3,2-b]-1,5-naphthyridine, 1H-indolo[3,2-b][1,7]naphthyridine, 1H-indolo[3,2-b][1,8]naphthyridine, 1H-indolo[3,2-c][1,8]naphthyridine, indolo[2,3-a]quinolizine, indolo[2,3-b]quinolizine, indolo[3,2-a]quinolizine, indolo[3,2-b]quinolizine, pyrano[4xe2x80x2,3xe2x80x2:5,6]pyrido[3,4-b]indole, pyrido[4xe2x80x2,3xe2x80x2:4,5]pyrano[3,2-b]indole, pyrido[4xe2x80x2,3xe2x80x2:5,6]pyrano[2,3-b]indole, pyrido[4xe2x80x2,3xe2x80x2:5,6]pyrano[3,4-b]indole, 1H-indolo[2,3-c]isoquinoline, 1H-indolo[3,2-c]isoquinoline, 1H-indolo[2,3-c]quinoline, 1H-indolo[3,2-c]quinoline, 1H-pyrido[213-a]carbazole 1H-pyrido[2,3-b]carbazole, 1H-pyrido[2,3-c]carbazole, 1H-pyrido[3,2-a]carbazole, 1H-pyrido[3,2-b]carbazole, 1H-pyrido[3,2-c]carbazole, 1H-pyrido[3,4-a]carbazole, 1H-pyrido[3,4-b]carbazole, 1H-pyrido[3,4-c]carbazole, 1H-pyrido[4,3-a]carbazole, 1H-pyrido[4,3-b]carbazole, 1H-pyrido[4,3-c]carbazole, 1H-quindoline, 1H-quinindoline, 1H-pyrano[3xe2x80x2,4xe2x80x2:5,6]pyrano[4,3-b]indole, [1]benzopyrano[2,3-b]indole, [1]benzopyrano[3,2-b]indole, [1]benzopyrano[3,4-b]indole, [1]benzopyrano[4,3-b]indole, [2]benzopyrano[4,3-b]indole, pyrano[2,3-a]carbazole, pyrano[2,3-b]carbazole1 pyrano[2,3-c]carbazole, pyrano[3,2-a]carbazole, pyrano[3,2-c]carbazole, pyrano[3,4-a]carbazole, 1H-phosphinolino[4,3-b]indole, [1] benzothiopyrano[2,3-b]indole, [1]benzothiopyrano[3,2-b]indole, [1]benzothiopyrano[3,4-b]indole, [1]benzothiopyrano[4,3-b]indole, [2]benzothiopyrano[4,3-b]indole, 1H-benzo[a]carbazole, 1H-benzo[b]carbazole, 1H-benzo[c]carbazole, [1,6,2]oxathiazepino[2xe2x80x2,3xe2x80x2:1,2]pyrido[3,4-b]indole, 1H-azepino[1xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, 1H-pyrido[1xe2x80x2,2xe2x80x2:1,2]azepino[4,5-b]indole, 2H-pyrido[1xe2x80x2,2xe2x80x2:1,2]azepino[3,4-b]indole, 1H-pyrido[3xe2x80x2,2xe2x80x2:5,6]oxepino[3,2-b]indole, 1H-pyrido[4xe2x80x2,3xe2x80x2:5,6]oxepino[3,2-b]indole, 2H-pyrido[2xe2x80x2,3xe2x80x2:5,6]oxepino[2,3-b]indole, 2H-pyrido[2xe2x80x2,3xe2x80x2:5,6]oxepino[3,2-b]indole, 2H-pyrido[3xe2x80x2,4xe2x80x2:5,6]oxepino[3,2-b]indole, pyrido[2xe2x80x2,3xe2x80x2:4,5]cyclohepta[1,2-b]indole, pyrido[3xe2x80x2,2xe2x80x2:3,4]cyclohepta[1,2-b]indole, pyrido[3xe2x80x2,4xe2x80x2:4,5]cyclohepta[1,2-b]indole, pyrido[3xe2x80x2,4xe2x80x2:5,6]cyclohepta[1,2-b]indole, 2H-pyrano[3xe2x80x2,2xe2x80x2:2,3]azepino[4,5-b]indole, 1H-indolo[3,2-b][1,5]benzoxazepine, 1H-indolo[3,2-d][1,2]benzoxazepine, 1H-indolo[2,3-c][1,5]benzothiazepine, [1,4]diazepino[2,3-a]carbazole, indolo[2,3-b][1,5]benzodiazepine, indolo[2,3-d][1,3]benzodiazepine, indolo[3,2-b][1,4]benzodiazepine, indolo[3,2-b][1,5]benzodiazepine, indolo[3,2-d][1,3]benzodiazepine, indolo[3,2-d][2,3]benzodiazepine, indolo[2,3-a][3]benzazepine, indolo[2,3-c][1]benzazepine, indolo[2,3-d][1]benzazepine, indolo[2,3-d][2]benzazepine, indolo[3,2-b][l]benzazepine, indolo[3,2-c][1]benzazepine, indolo[3,2-d][1]benzazepine, 1H-indolo[2,1-b][3]benzazepine, 1H-[1]benzoxepino[5,4-b]indole, 1H-[2]benzoxepino[4,3-b]indole, 1H-[1]benzothiepino[4,5-b]indole, 1H-[l]benzothiepino[5,4-b]indole, benzo[3,4]cyclohepta[1,2-b]indole, benzo[4,5]cyclohepta[1,2-b]indole, benzo[5,6]cyclohepta[1,2-b]indole, benzo[6,7]cyclohepta[1,2-b]indole, cyclohepta[b]carbazole, 4H-[1,5]oxazocino[5xe2x80x2,4xe2x80x2:1,6]pyrido[3,4-b]indole, azocino[1xe2x80x2,2xe2x80x2:1,2]pyrido[3,4-b]indole, 2,6-methano-2H-azecino[4,3-b]indole, 3,7-methano-3H-azecino[5,4-b]indole, pyrido[1xe2x80x2,2xe2x80x2:1,8]azocino[5,4-b]indole, pyrido[4xe2x80x2,3xe2x80x2:6,7]oxocino[2,3-b]indole, pyrido[4xe2x80x2,3xe2x80x2:6,7]oxocino[4,3-b]indole, 1,5-methano-1H-azecino[3,4-b]indole, 2,6-methano-1H-azecino[5,4-b,]indole, 1H-pyrido[3xe2x80x2,4xe2x80x2:5,6]cycloocta[1,2-b]indole, 1,4-ethanooxocino[3,4-b]indole, pyrano[3xe2x80x2,4xe2x80x2:5,6]cycloocta [1,2-b]indole, 1H-indolo[2,3-c][1,2,5,6]benzotetrazocine, 1H-indolo[2,3-c][1,6]benzodiazocine, 6,13b-methano-13bH-azecino[5,4-b]indole, oxocino[3,2-a]carbazole, 1H-benzo[g]cycloocta[b]indole, 6,3-(iminomethano)-2H-1,4-thiazonino[9,8-b]indole, 1H,3H-[1,4]oxazonino[4xe2x80x2,3xe2x80x2:1,2]pyrido[3,4-b]indole, 2H-3,6-ethanoazonino[5,4-b]indole, 2H-3,7-methanoazacycloundecino[5,4-b]indole, 1H-6,12b-ethanoazonino[5,4-b]indole, indolo[3,2-e][2]benzazonine, 5,9-methanoazacycloundecino[5,4-b]-indole, 3,6-ethano-3H-azecino[5,4-b]indole, 3,7-imethano-3H-azacycloundecino[5,4-b]indole, pyrano[4xe2x80x2,3xe2x80x2:8,9]azecino[5,4-b]indole, 1H-indolo[2,3-c][1,7]benzodiazecine, 1H-indolo[3,2-e][2]benzazecine, benzo]pyrrolo[3,2-b]indole, benzo[e]pyrrolo[3,2-g]indole, benzo[e]pyrrolo[3,2,1-hi]indole, benzo[e]pyrrolo[3,4-b]indole, benzo[g]pyrrolo[3,4-b]indole, 1H-benzo[f]pyrrolo[1,2-a]indole, 1H-benzo[g]pyrrolo[1,2-a]indole, 2H-benzo[e]pyrrolo[1,2-a]indole, 1H-benzo[f]pyrrolo[2,1-a]isoindole, 1H-benzo[g]pyrrolo[2,1-a]isoindole, 2H-benzo[e]pyrrolo[2,1-a]isoindole, isoindolo[6,7,1-cde]indole, spiro[cyclohexane-1,5xe2x80x2-[5H]pyrrolo[2,1-a]isoindole], isoindolo[7,1,2-hij]quinoline, 7,11-methanoazocino[1,2-a]indole, 7,11-methanoazocino[2,1-a]isoindole, dibenz[cd,f]indole, dibenz[cd,g]indole, dibenz[d,f]indole, 1H-dibenz[e,g]indole, 1H-dibenz[e,g]isoindole, naphth[1,2,3-cd]indole, naphth[1,8-ef]indole, naphth[1,8-fg]indole, naphth[3,2,1-cd]indole, 1H-naphth[1,2-e]indole, 1H-naphth[1,2-f]indole, 1H-naphth[1,2-g]indole, 1H-naphth[2,1-e]indole, 1H-naphth[2,3-e]indole, 1H-naphth[1,2-f]isoindole, 1H-naphth[2,3-e]isoindole, spiro[1H-carbazole-1,1xe2x80x2-cyclohexane], spiro[2H-carbazole-2,1xe2x80x2-cyclohexane], spiro[3H-carbazole-3,1xe2x80x2-cyclohexane], cyclohepta[4,5]pyrrolo[3,2-f]quinoline, cyclohepta[4,5]pyrrolo[3,2-h]quinoline, azepino[4,5-b]benz[e]indole, 1H-azepino[1,2-a]benz[f]indole, 1H-azepino[2,1-a]benz[f]isoindole, benzo[e]cyclohepta[b]indole, and benzo[g]cyclohepta[b]indole;
(5) the phenyl group fused to a tricyclic hetero system: 
xe2x80x83wherein ----- represents a single bond or a double bond; ring Exe2x80x2 and ring Fxe2x80x2 are as defined hereinafter, which corresponds to the group available upon elimination of one hydrogen atom from a tetracyclic hetero ring system and, as such, includes but is not limited to 1H-dipyrrolo[2,3-b:3xe2x80x2,2xe2x80x2,1xe2x80x2-hi]indole, spiro[cyclopentane-1,2xe2x80x2(1xe2x80x2H)-pyrrolo[3,2,1-hi]indole], spiro[imidazolidine-4,1xe2x80x2(2xe2x80x2H)-[4H]pyrrolo[3,2,1-ij]quinoline], pyrido[2,3-b]pyrrolo[3,2,1-hi]indole, pyrido[4,3-b]pyrrolo[3,2,1-hi]indole, benzo[de]pyrrolo[3,2,1-ij]quinoline, 3H-pyrrolo[3,2,1-de]acridine, 1H-pyrrolo[3,2,1-de]phenanthridine, spiro[cyclohexane-1,6xe2x80x2-[6H]pyrrolo[3,2,1-ij]quinoline], 4,9-methanopyrrolo[3,2,1-1m][1]benzazocine, spiro[cycloheptane-1,6xe2x80x2-[6H]pyrrolo[3,2,1-ij]quinoline], 1H-pyrano[3,4-d]pyrrolo[3,2,1-jk][1]benzazepine, 3H-benzo[b]pyrrolo[3,2,1-jk][4,1]benzoxazepine, 7H-indolo[1,7-ab][4,1]benzoxazepine, benzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine, indolo[1,7-ab][1,4]benzodiazepine, indolo[1,7-ab][1]benzazepine, indolo[7,1-ab][3]benzazepine, 1H-cyclohepta[d][3,2,1-jk][1]benzazepine, spiro[azepino[3,2,1-hi]indole-7(4H),1xe2x80x2-cycloheptane], 4H-5,11-methanopyrrolo[3,2,1-no][1]benzazacycloundecine, spiro[azepino[3,2,1-hi]indole-7(4H),1xe2x80x2-cyclooctane], and so forth.
The xe2x80x9cphenyl group fused to a tricyclic hetero systemxe2x80x9d includes not only the phenyl group fused to tricyclic hetero systems containing an optionally hydrogenated indole or isoindole ring but also the phenyl group fused to the following and other tricyclic hetero systems, inclusive of the corresponding dihydro, tetrahydro, hexahydro, octahydro, and decahydro compounds. For example, fluoranthene, acephenanthrylene, aceanthrylene, triphenylene, pyrene, chrysene, naphthacene, pleiadene, benz[a]anthracene, indeno[1,2-a]indene, cyclopenta[a]phenanthrene, pyrido[1xe2x80x2,2xe2x80x2:1,2]imidazo[4,5-b]quinoxaline, 1H-2-oxapyrene, spiro[piperidine-4,9xe2x80x2-xanthene], etc. can be mentioned.
The preferred group which is formed as the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d is fused to a tricyclic hetero system which may be substituted includes groups of the following formulas. 
wherein ring Exe2x80x2, ring Fxe2x80x2, and ring Gxe2x80x2 independently represent a 5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxo in addition to R1, ring A, ring F, ring G are as defined hereinbefore.
Particularly preferred is the group of the formula: 
The xe2x80x9c5- to 9-membered nitrogen-containing hetero ring xe2x80x9d of the xe2x80x9c5- to 9-membered nitrogen-containing hetero ring which may be substituted by oxoxe2x80x9d includes the rings specifically mentioned for the xe2x80x9c5- to 9-membered nitrogen-containing hetero ringxe2x80x9d for ring Cxe2x80x2 and ring Dxe2x80x2.
The preferred group which is formed as (2) the xe2x80x9cphenyl groupxe2x80x9d of the xe2x80x9cphenyl group which may be, substituted and/or condensedxe2x80x9d for Ar is fused to a bicyclic hetero system which may be substituted or two similar or dissimilar monocyclic rings (at least one of the two rings is a monocyclic hetero ring) which may be substituted and (3) the xe2x80x9cphenyl groupxe2x80x9d is fused to a tricyclic hetero system include the following groups: 
wherein the respective symbols are as defined hereinbefore.
Particularly preferred examples of the xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d for Ar are groups of the following formula: 
wherein R1 is as defined hereinbefore.
For the best result, xe2x80x9cphenyl group which may be substituted and/or condensedxe2x80x9d for Ar are groups of the following formula: 
wherein R1 is as defined hereinbefore.
In the formula, n represents an integer of 1 to 10, preferably 1 to 6, and more preferably 2 to 6, furtheremore preferably 3 to 6, for the best result 3, 4 or 5.
In the formula, R represents hydrogen atom or a hydrocarbon group which may be substituted, which may not be the same in its n occurrences.
The xe2x80x9chydrocarbon groupxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the hydrocarbon group which may be substitutedxe2x80x9d for R have the same meanings as the xe2x80x9chydrocarbon groupxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d, which has been mentioned for R1.
R may be bound to Ar or a substituent on Ar.
The compound of formula (I) wherein R is bound to Ar or a substituent or Ar includes compounds of the formula: 
wherein R1, n, and Y are as defined hereinbefore, compounds of the formula: 
wherein n and Y are as defined hereinbefore, and compounds of the formula: 
wherein n and Y are as defined hereinbefore.
Preferably, R is hydrogen atom.
In the formula, Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted.
The xe2x80x9camino group which may be substitutedxe2x80x9d for Y includes but is not limited to groups of the formula: 
wherein R4 and R5 may be the same or different and each represents hydrogen atom, a hydrocarbon group which may be substituted, or an acyl group.
The xe2x80x9chydrocarbon groupxe2x80x9d of, and xe2x80x9csubstituentxe2x80x9d on, the hydrocarbon group which may be substitutedxe2x80x9d for R4 and R5 includes but is not limited to the respective species mentioned for the xe2x80x9chydrocarbon groupxe2x80x9d and xe2x80x9csubstituentxe2x80x9d for R1.
The preferred hydrocarbon group which may be substituted as represented by R4 and R5 includes (1) a straight-chain or branched lower alkyl groups (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc.) which may have 1 to 3 substituent groups selected from the group cinsisting of, (i) halogen (e.g. fluorine, chlorine, bromine, iodine), (ii) lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, etc.), and (iii) hydroxy, and so on, and (2) lower aralkyl (e.g. C7-16 aralkyl such as phenyl-C1-10 alkyl (such as benzyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, etc.), naphthyl-C1-6 alkyl (such as a-naphthylmethyl etc.), or diphenyl-C1-3 alkyl (such as diphenylmethyl, diphenylethyl, etc.), and so on), which may have 1 to 3 substituents selected from the group consisting of (i) halogen (e.g. fluorine, chlorine, bromine, iodine), (ii) lower alkoxy (e.g. C1-6 alkoxy such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, etc.), and (iii) hydroxy and so on.
The more preferred examples are (1) unsubstituted straight-chain or branched lower alkyl groups (e.g. C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc.) and (2) unsubstituted lower aralkyl groups such as C7-16 aralkyl (e.g. phenyl-C1-10 alkyl (such as benzyl, phenethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl, etc.), naphthyl-C1-6 alkyl (e.g. a-naphthylmethyl etc.) and diphenyl-C1-3 alkyl (e.g. diphenylmethyl, diphenylethyl, etc.), and so on.
The xe2x80x9cacyl groupxe2x80x9d for R4 and R5 includes but is not limited to the species mentioned for the xe2x80x9cacyl groupxe2x80x9d for R1.
The xe2x80x9cnitrogen-containing saturated heterocyclic groupxe2x80x9d of the xe2x80x9cnitrogen-containing saturated heterocyclic group which may be substitutedxe2x80x9d for Y includes 5- to 9-membered nitrogen-containing saturated heterocyclic groups optionally containing 1 to 3 hetero atoms, such as nitrogen, oxygen and/or sulfur, in addition to carbon and one nitrogen atom. Each of those nitrogen-containing saturated heterocyclic groups may have a valence bond on a ring nitrogen atom or on a ring carbon atom. The group having a valence bond on a ring nitrogen atom includes groups of the formula: 
wherein ring Q1 represents a 5- to 9-membered nitrogen-containing saturated heterocyclic group which may contain 1 or 2 hetero atoms selected from among nitrogen, oxygen, sulfur, etc. in addition to carbon and one nitrogen atom. More specifically, the following groups can be generally selected: 
The group having a valence bond on a ring carbon atom includes but is not limited to groups of the formula: 
wherein ring Q2 represents a 5- to 9-membered nitrogen-containing saturated heterocyclic group which may contain 1 or 2 hetero atoms selected from among nitrogen, oxygen, sulfur, etc. in addition to carbon and one nitrogen atom. Preferred examples are groups of the following formulas: 
The xe2x80x9csubstituentxe2x80x9d that may-be present on the xe2x80x9cnitrogen-containing saturated heterocyclic group which may be substitutedxe2x80x9d, as mentioned for Y, includes (1) those groups specifically mentioned for the xe2x80x9csubstituentxe2x80x9d on the xe2x80x9cnitrogen-containing hetero ring which may be substitutedxe2x80x9d which may be formed by R2 and R3 in combination with the adjacent nitrogen atom, and (2) the groups mentioned for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d, the xe2x80x9cacyl groupxe2x80x9d, and the xe2x80x9cheterocyclic group which may be substitutedxe2x80x9d for R1.
The preferred xe2x80x9cnitrogen-containing saturated heterocyclic groupxe2x80x9d of the xe2x80x9cnitrogen-containing saturated heterocyclic group which may be substitutedxe2x80x9d for Y includes 4-piperidinyl, 1-piperidinyl, or 1-piperazinyl.
Preferably, Y represents a group of the formula: 
wherein R6 represents the group same as defined for R1.
More preferably, Y represents a group of the formula: 
wherein R6 represents (i) a phenyl-C1-6 alkyl group which may be substituted by C1-6 alkyl, C1-6 alkoxy, halogen, nitro, mono- or di-C1-6 alkyl-carbamoyloxy, hydroxy, cyano, carboxyl, C1-6 alkoxy-carbonyl, carbamoyl, mono-lower alkyl-carbamoyl, di-lower alkyl-carbamoyl, cyclicamino-carbonyl which may be substituted, amino, mono-lower alkylamino, di-lower alkylamino, 5- to 7-membered cyclic amino which may contain 1 to 3 hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur, in addition to carbon and one nitrogen atom, C1-6 alkyl-carbonylamino, phenylsulfonylamino, C1-6 alkyl-sulfonylamino, amidino, ureido, or heterocyclic ring (the above mentioned C1-6 alkyl, C1-6 alkoxy, carbamoyl, cyclicamino-carbonyl, amino, phenylsulfonylamino, amidino, ureido, an d heterocyclic ring may be still substituted by the xe2x80x9csubstituenttxe2x80x9d for the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d which has been mentioned for R1), (ii)a hydrogen atom, (iii) a C1-6 alkyl group which may be substituted by halogen, hydroxy, C1-6 alkoxy, amino, mono- or di-C1-6 alkylamino, carboxyl, cyano or C1-6 alkoxy-carbonyl, or (iv)a C1-6 alkyl-carbonyl group which may be substituted by mono-or di-C1-6 alkyl-amino or C1-6 alkoxy-carbonyl, preferably R6 represents a benzyl group which may be substituted, the substitutent being selected from the group consisting of C1-4 alkyl (e.g. methyl etc.), trihalogeno (e.g. fluoro etc.)-C1-4 alkyl (e.g. methyl etc.), halogen (e.g. fluoro, chloro etc.), nitro, cyano, C1-4 alkoxy,(e.g. methoxy etc.), hydroxy, carbamoyl, (4-C1-4 alkyl (e.g. methyl etc.)piperazinyl)carbonyl, morpholinocarbonyl, carboxyl, C1-4 alkoxy (e.g. methoxy etc.)carbonyl, C1-4 alkoxy (e.g. ethoxy etc.)carbonyl-C1-4 alkoxy (e.g. methoxy etc.), carboxyl-C1-4 alkoxy (e.g. methoxy etc.), C1-4 alkoxy (e.g. ethoxy etc.)carbonyl-C1-6 alkyl (e.g. isopropyl etc.), carboxyl-C16alkyl (e.g. isopropyl etc.), amino, acetylamino, C1-4 alkyl (e.g. methyl etc.)sulfonylamino, (4-C1-4 alkyl (e.g. methyl etc.)phenyl)sulfonylamino, ureido, 3-C1-4 alkyl (e.g. methyl etc.)ureido, amidino, dihydrothiazolyl, or dihydroimidazolyl, more preferably R6 represents a benzyl group which may be substituted by C1-4 alkyl (e.g. methyl etc.), trihalogeno (e.g. fluoro etc.)-C1-4 alkyl (e.g. methyl etc.), halogen (e.g. fluoro, chloro etc.), nitro, hydroxy, carbamoyl, amino, amidino, dihydroimidazolyl.
Particularly, Y is a group most usually selected from the group consisting of 1-benzyl-4-piperidihyl, 4-benzyl-1-piperidinyl, 4-benzyl-1-piperazinyl, 1-acetyl-4-piperidinyl, 1-[(2-methylphenyl)methyl]-4-piperidinyl, 1-[(3-chlorophenyl)methyl]-4-piperidinyl, 1-[(2-chlorophenyl)methyl]-4-piperidinyl, 1-[(3-nitrophenyl)methyl]-4-piperidinyl, 1-[(3-(trifluoromethyl)phenyl)methyl]-4-piperidinyl are preferred, with 1-benzyl-4-piperidinyl, 1-acetyl-4-piperidinyl, 1-[(2-methylphenyl)methyl]-4-piperidinyl, 1-[(3-chlorophenyl)methyl]-4-piperidinyl, 1-[(2-chlorophenyl)methyl]-4-piperidinyl, 1-[(3-nitrophenyl)methyl]-4-piperidinyl, 1-[[3-(trifluoromethyl)phenyl]methyl]-4-piperidinyl.
For the best result, Y represents a group of the formula: 
wherein R6 is as defined hereinbefore, for the still best result, 1-acetyl-4-piperidinyl, 1-[(2-methylphenyl)methyl]-4-piperidinyl, 1-[(3-chlorophenyl)methy]-4-piperidinyl, 1-[(2-chlorophenyl)methy]-4-piperidinyl can be used.
Among compounds of formula (I), the preferred compounds are such that
Ar represents a group of the formula: 
wherein R1 represents (i) hydrogen atom, (ii) a C1-6 alkyl group, (iii) a phenyl-C1-6 alkyl group which may be substituted by C1-6 alkyl, C1-6 alkoxy, halogen, or nitro, or (iv) xe2x80x94(C=O)-R2xe2x80x2 (R2xe2x80x2 represents a phenyl or phenyl-C1-6 alkyl group, which may be substituted by C1-6 alkyl or C1-6 alkoxy);
n is 2,3 or 4;
R represents hydrogen atom; and
Y represents a group of the formula: 
wherein R6 represents a phenyl-C1-6 alkyl group which may be substituted by C1-6 alkyl, C1-6 alkoxy, halogen, nitro, mono- or di-C1-6 alkyl-carbamoyloxy, (ii) hydrogen atom, (iii) a C1-6 alkyl group which may be substituted by halogen, hydroxy, C1-6 alkoxy, amino, mono- or di-C1-6 alkylamino, carboxyl, or C1-6 alkoxy-carbonyl, or (iv) a C1-6 alkyl-carbonyl group.
More specifically, the following compounds of the compound categories (I), inclusive of their salts, are preferred.
In the above chemical formulas of Compound 1 to Compound 61, Me stands for methyl, Et for ethyl, Bu for butyl, Pr for propyl, iPr for isopropyl, Pen for pentyl, MeO for methoxy, Ph for phenyl, and Ac for acetyl.
The compounds of the following formulas: 
wherein R1 represents a hydrogen atom, a hydrocarbon group which maybe substituted, an acyl group, or a heterocyclic group which may be substituted; n represents an integer of 1 to 10; Y represents an amino group which may be substituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof, are more preferred.
The salt of said compound (I), (Ia), (Ib), or (Ic) is preferably a biologically acceptable acid addition salt. The salt, thus, includes salts with inorganic acids (such as hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, etc.) and salts with organic acids (such as acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, etc.).
In addition, in cases compound (I) of the present invention has an acidic group such as xe2x80x94COOH, the compound (I) may form salts with inorganic bases (such as sodium, potassium, calcium, magnesium,etc.) ammonia, etc. or organic bases (such as triethylamine etc.). Such salts are also subsumed in the concept of the objective compound of the present invention.
Furthermore, said compound (I) may be a hydrate or an anhydrous compound.
Compound (I) and its salts, mentioned above, can be produced in accordance with the per se known processes. Referring to the formula,
(1) where the xe2x80x9cphenyl which may be substituted and/or condensedxe2x80x9d for Ar does not form a fused ring system, the process described in Japanese Patent Unexamined Publication No. 173867/1991 (EP-A-0378207) or Japanese Patent Unexamined Publication No. 79151/1989 (EP-A-0296560) can be used.
(2) where the xe2x80x9cphenyl which may be substituted and/or condensedxe2x80x9d for Ar is fused to a monocyclic hetero ring which may be substituted, the process described in Japanese Patent Unexamined Publication No. 140149 /1993 (EP-A-0487071), Japanese Patent Unexamined Publication No. 166676/1994 (EP-A-0560235), Japanese Patent Unexamined Publication No. 206875/1994 (EP-A-0567090) or Japanese Patent Unexamined Publication No. 169569/1990 (U.S. Pat. No. 4,895,841) can be used.
(3) where the xe2x80x9cphenyl which may be substituted and/or condensedxe2x80x9d for Ar is fused to a bicyclic hetero system which may be substituted or two similar or dissimilar monocyclic rings (at least one of the two rings is a monocyclic hetero ring) which may be substituted, the process described in Japanese Patent Unexamined Publication No. 206854/1995 (EP-A-0607864) can be used.
(4) where the xe2x80x9cphenyl which may be substituted and/or condensed for Ar is fused to a tricyclic hetero system which may be substituted, the process described in Japanese Patent Unexamined Publication No. 309835/1995 (EP-A-0655451) can be used.
A method of producing the compound (Ia), (Ib), (Ic) or a salt thereof is hereinafter described in detail.
Although the following description of the production process is applicable not only to the compound (Ia), (Ib), (Ic) themselves but also to the above-described salt thereof, the salt is also referred to as the compound (Ia-c) in the description below.
The compound (Ia-c) can be produced by reacting
(1), a compound represented,by the formula:
Arxe2x80x94Hxe2x80x83xe2x80x83(II)
xe2x80x83wherein Ar represents the group represented by following formulas: 
xe2x80x83for the production of (Ia), 
xe2x80x83for the production of (Ib), 
xe2x80x83for the production of (Ic), or salt thereof, and (2) a compound represented by the formula: 
xe2x80x83wherein Z1 represents a leaving group; the other symbols have the same definitions as above or a salt thereof.
The leaving group for Z1 is exemplified by a halogen atom (e.g., chlorine, bromine, iodine etc.), a C1-6 alkylsulfonyloxy group (e.g., methanesulfonyloxy, ethanesulfonyloxy etc.) or a C6-10 arylsulfonyloxy group (e.g., benzenesulfonyloxy, p-toluenesulfonyloxy etc.), with preference given to a halogen atom (e.g., chlorine etc.) and others.
The compound (II) or a salt thereof can be produced by known methods or modifications thereof such as the methods described in Indian Journal of Chemistry, 2, 211(1964), Indian Journal of Chemistry, 12, 247(1974), Bulletin of The Chemical Society of Japan, 43,1824(1970), Chemical Pharmaceutical Bulletin, 20, 1328(1972), Chemical Pharmaceutical Bulletin, 27, 1982(1979), Helvetica Chimica Acta, 46, 1696(1963), Synthesis,541(1979), U.S. Pat. No. 3,682,962, U.S. Pat. No. 3,911,126, Ger.Offen. 2,314,392, Ger. 1,545,805, Journal of Chemical Society, 1381(1949), Canadian Journal of Chemistry, 42, 2904(1964), Journal of Organic Chemistry, 28, 3058(1963), Journal of American Chemical Society, 76, 3194(1954), 87, 1397(1965), 88, 4061(1966) and Japanese Patent Unexamined Publication No. 41539/1974.
The compound (III) or a salt thereof can be produced by known methods or modifications thereof such as the methods described in Chemical Pharmaceutical Bulletin, 41, 529-538(1993), Chemical Pharmaceutical Bulletin, 34, 3747-3761(1986) and EP-A-0,378,207.
Salts of the compounds (II) and (III) include salts with inorganic acids (e.g., hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid etc.) and salts with organic acids (e.g., acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid etc.). When having an acidic group such as xe2x80x94COOH, the compounds (II) and (III) may form a salt with an inorganic base (e.g., alkaline metal or alkaline earth metal (e.g., sodium, potassium, calcium, magnesium etc.), ammonia etc.) or an organic base (e.g., tri-C1-3 alkylamine such as triethylamine etc.).
The reaction between the compound (III) or a salt thereof and the compound (II) or a salt thereof can be carried out by, for example, reacting them in the absence of a solvent or in a solvent as necessary. Any solvent for ordinary chemical represents can be used for this reaction, as long as the reaction is not interfered with the reaction. Such solvents include organic solvents such as hydrocarbon solvents (e.g., pentane, hexane, benzene, toluene, nitrobenzene etc.), halogenated hydrocarbon solvents (e.g., dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride etc.), ether solvents (e.g., ethyl ether, tetrahydrofuran, dioxane, diemthoxyethane etc.), nitroalkanes (e.g., nitromethane, nitroethane etc.), and carbon disulfide, with preference given to dichloromethane, 1,2-dichloroethane, nitrobenzene, carbon disulfide and others. The amount of solvent used is normally about 0.5 to about 100 ml, preferably about 5 to about 20 ml per mmol of the compound (III) or a salt thereof. Reaction temperature is normally about xe2x88x9230 to about 150xc2x0 C., preferably about 20 to about 100xc2x0 C. Reaction time is normally about 0.5 to about 72 hours, preferably about 1 to about 16 hours.
Lewis acids can be used in this rection if necessary. Such lewis acids include aluminum chloride, aluminum bromide, zinc chloride, titanium chloride, tin (IV) chloride, boron trifluoride, iron (II) chloride, iron (III) chloride, antimony (V) pentachloride, bismuth (III) chloride, mercury (II) chloride, hydrogen fluoride, sulfuric acid and polyphosphoric acid, with preference given to aluminum chloride and others. The amount of Lewis acid used is normally about 1 to about 10 mol, preferably about 2 to about 10 mol per mol of the compound (III) or a salt thereof. The amount of the compound (II) or a salt thereof used is normally about 1 to about 20 mol, preferably about 1 to about 5 mol per mol of the compound (III) or a salt thereof.
In the above reaction, the position at which the following group: 
in the compound (III) or a salt thereof is introduced to the compound (II) or a salt thereof may be any one of the possible positions of substitution in ring A. However, when the compound (II) or a salt thereof has a 2,3,4,5-tetrahydro-1H-2-benzazepine skeleton(provided that ring A has no substituent), it is introduced mainly at the 8-position. However, compounds having an introduction at other positions (6-,7- or 9-positions) may be produced and separated.
With respect to the above reactions, provided that the starting material compound has an amino group, a carboxyl group, a hydroxy group or another group as a substituent therefor, such substituent may have a protecting group in common use in peptide chemistry etc. as introduced therein. The desired compound can be obtained by removing the protecting group as necessary completion of the reaction.
Protecting groups for the amino group include a form group a C1-6 alkyl-carbonyl group which may be substituted (e.g., acetyl, ethylcarbonyl etc.), a benzyl group, a C1-6 alkyl-oxycarbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl etc.), a phenyloxycarbonyl, group (e.g., phenoxycarbonyl etc.), an acyl group such as a C7-15alkyloxy-carbonyl group (e.g., b genyloxycarbonyl, fluorenyloxycarbonyl etc.), a hydrocarbon group ( e.g. trityl, phthaloyl, etc.). Substituents for these protecting groups include halogen atom (e.g., fluorine, chlorine, bromine, iodine etc.), C1-6 alkyl-carbonyl (e.g., methylcarbonyl, ethylcarbonyl, butylcarbonyl etc.) and nitro, the number of substituents being about 1 to about 3. Protecting groups for the carboxyl group include a C1-6 alkyl group which may be substituted (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl etc.), a phenyl group, a trityl group and a silyl group. Substituents for these protecting groups include halogen (e.g., fluorine, chlorine, bromine or iodine etc.), formyl, C1-6 alkyl-carbonyl (e.g., methylcarbonyl, ethylcarbonyl, butylcarbonyl etc.) and nitro, the number of substituents being about 1 to about 3.
Protecting groups for the hydroxyl group include a C1-6 alkyl group which may be substituted (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl eta.), a phenyl group, a C7-10 aralkyl group (e.g, benzyl etc.), a formyl group, a C1-6 alkylcarbonyl group (e.g., acetyl, ethylcarbonyl etc.), a phenyloxycarbonyl group (e.g., phenoxycarbonyl etc.), a C7-10 aralkyl-carbonyl group (e.g., benzyloxycarbonyl etc.), a pyranyl group, a furanyl group and a silyl group. Substituents for these protecting groups include halogen (e.g., fluorine, chlorine, bromine, iodine etc.), C1-6 alkyl, phenyl, C7-10 aralkyl and nitro, the number of substituents being about 1 to 4.
These protecting groups can be removed by known methods or modifications thereof, including treatments With acid, base, reducing agents, ultraviolet rays, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride and palladium acetate.
When the compound (Ia-c) or a salt thereof thus obtained has an acylamino group which may be substituted, it can be converted to a compound or a salt thereof having a primary or secondary amino group by deacylation. The starting material compound (Ia-c) or a salt thereof having an acylamino group which may be substituted may be as isolated and purified by known means such as concentration, liquid property conversion, redissolution, solvent extraction, fractional distillation, distillation, crystallization, recrystallization and chromatography, or may be used in the form of a reaction mixture as such, without isolation, as a starting material. Accordingly, the compound (Ia-c) or a salt thereof having an acylamino group which may be substituted is kept at a temperature of normally about 10 to about 150xc2x0 C., preferably about 50 to about 100xc2x0 C., in an aqueous solution of antacid such as a mineral acid (e.g., nitric acid, hydrochloric acid, hydrobromic acid, iodic acid, sulfuric acid etc.) or a base such as an alkaline metal hydroxide ((e.g., sodium hydroxide, potassium hydroxide, barium hydroxide, lithium hydroxide etc.). The amount of such acid or base used is normally about 1 to about 100 mol, preferably about 1 to about 40 mol per mol of the compound (XII) or a salt thereof. The strength of acid or base is normally about about 0.1 to about 10 N, preferably about 2 to about 10 N. Although varying depending on reaction temperature, reaction time is normally about 1 to about 24 hours, preferably about 2 to about 10 hours.
By means of introducing a hydrocarbon group which may be substituted to a primary or secondary amino group of the thus-obtained compound (Ia-c) or a salt thereof, the compound (Ia-c) or a salt thereof having an amino group which may be substituted for by hydrocarbon which may be substituted was produced. The starting material compound (Ia-c) or a salt thereof having an primary or secondary amino group may be used after isolation and purification by known means such as concentration, liquid property conversion, redissolution, solvent extraction, fractional distillation, distillation, crystallization, recrystallization and chromatography, or may be used in the form of a reaction mixture as such, without isolation, as a starting material. Accordingly, the compound (Ia-c) or a salt thereof having an amino group substituted for by hydrocarbon which may be substituted can also be produced by reaction between the compound (Ia-c) or a salt thereof having a primary or secondary amino group and a compound represented by the formula:
R7xe2x80x94Z3xe2x80x83xe2x80x83(XIII)
wherein R7 represents a hydrocarbon group which may be substituted; Z3 represents a leaving group.
The optionally substituted hydrocarbon group for R7 is exemplified by the same optionally substituted hydrocarbon groups as specified for R1 or R6 above.
The leaving group for Z3 is exemplified by a halogen atom (e.g., chlorine, bromine and iodine etc.), a C1-6 alkylsulfonyloxy group (e.g., methanesulfonyloxy, ethanesulfonyloxy etc.) or a C6-10 arylsufonyloxy group (e.g., benzenesulfonyloxy, p-toluenesulfonyloxy etc.), with preference given to methanesulfonyloxy, or a halogen atom (e.g., chlorine, bromine etc.).
This reaction can be carried out in the presence or absence of a solvent, with a base added as necessary. Bases for this purpose include inorganic bases such as sodium carbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide and sodium hydride, and organic bases such as pyridine, 4-dimethylaminopyridine and triethylamine. Any solvent can be used, as long as it does not interfere with the reaction, such solvents include lower alcohols such as methanol, ethanol, propanol, isopropanol, n-butanol and t-butanol, ethers such as dioxane, ether and tetrahydrofuran, aromatic hydrocarbons such as toluene, benzene and xylene, halogenated hydrocarbons such dichloromethane, 1,2-dichloroethane, amides such as dimethylformamide, dimethylacetamide and hexamethylphosphonotriamide, esters such as ethyl acetate and butyl acetate and nitrites such as acetonitrile and propionitrile. This reaction can be carried out under cooling conditions (about 0 to about 10xc2x0 C.), at room temperature (about 10 to about 40xc2x0 C.) or under heating conditions (about 40 to about 120xc2x0 C.). Reaction time is normally about 10 minutes to about 48 hours, preferably about 2 to about 16 hours. The amount of compound (XIII) used is preferably about 0.3 to about 5.0 mol per mol of the compound (Ia-c) or a salt thereof having a primary or secondary amino group. The amount of base used is normally about 1 or more mol, preferably about 1.1 to about 5 mol per mol of the compound (Ia-c) or a salt thereof having a primary or secondary amino group.
Also this reaction may be accelerated as appropriate in the presence of an iodide such as sodium iodide, potassium iodide or lithium iodide. In this case, the amount of iodide used is normally about 1 to about 5 mol, preferably about 1.1 to about 1.5 mol per mol of the compound (XIII).
The compound (XIII) can be produced by known method or modifications thereof.
The compound (Ia-c) thus obtained can be converted to a salt by a conventional method when it is in a free form, and can be converted to a free form or another salt by a conventional method when it is in a salt form. The compound (Ia-c) or a salt thereof can be isolated and purified by known methods as described above. Also, the compound (Ia-c) or a salt thereof involves steric isomers based on the presence-of asymmetric carbon atoms. These isomers can also be isolated and purified by known methods as described above or other methods such as fractional recrystallization, and chromatography using optically active columns.
The following compounds of the compound categories (I), inclusive of their salts, are preferred novel compound. 
wherein R1 is as defined hereinbefore; R6 represents the group same as defined for R1;n represents an integer of 3 to 6.
The prefered novel compounds (Ia2), (Ib2) and (Ic2) or salts thereof can be can be produced in accordance with the per se known processes (e.g. EP-A-0487071, EP-A-0567090, etc.) or modifications thereof.
A method of producing the compound (Ia2) or a salt thereof is hereinafter described in detail.
Although the following description of the production process is applicable not only to the compound (Ia2) itself but also to the above-described salt thereof, the salt is also6referred to as the compound (Ia2) in the description below.
The compound (Ia2: R6=W or H) can be produced by reacting a compound represented by the formula: 
wherein R1 is defined as hereinbefore, or sart thereof, with a compound represented by the formula: 
wherein Z1 represents a leaving group; W represents a protective group; n represents an integer of 3 to 6, if necessary, followed by deprotectioning reaction.
The leaving group for Z1 is exemplified by a halogen atom (e.g., chlorine, bromine, iodine etc.), a C1-6 alkylsulfonyloxy group (e.g., methanesulfonyloxy, ethanesulfonyloxy etc.) or a C6-10 arylsulfonyloxy group (e.g., benzenesulfonyloxy, p-toluenesulfonyloxy etc.), with preference given to a halogen atom (e.g., chlorine etc.) and others.
The compound (IIa) or a salt thereof can be produced by known methods or modifications thereof such as the methods described in Journal of Organic Chemistry, 34, 2235(1969), Journal of Organic Chemistry, 54, 5574(1989), Tetrahedron Letters, 35, 3023(1977) and EP-A-0,487,071.
The compound (IIIa) or a salt thereof can be produced by known methods or modifications thereof such as the methods described in Chemical Pharmaceutical Bulletin, 41, 529-538(1993), Chemical Pharmaceutical Bulletin 34, Bulletin, 34, 3747-3761(1986), EP-A-0,378,207 and EP-A-0,487,071.
Salts of the compounds (IIa) and (IIIa) include salts with inorganic acids (e.g., hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid etc.) and salts with organic acids (e.g., acetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citric acid, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid etc.). When having an acidic group such as xe2x80x94COOH, the compounds (IIa) and (IIIa) may form a salt with an inorganic base (e.g., alkaline metal or alkaline earth metal(e.g., sodium, potassium, calcium, magnesium etc.), ammonia etc.) or an organic base (e.g., tri-C1-3 alkylamine such as triethylamine etc.).
The reaction between the compound (IIIa) or a salt thereof and the compound (IIa) or a salt thereof can be carried out by, for example, reacting them in the absence of a solvent or in a solvent as necessary. Any solvent for ordinary chemical represents can be used for this reaction, as long as the reaction is not interfered with the reaction. Such solvents include organic solvents such as hydrocarbon solvents (e.g., pentane, hexane, benzene, toluene, nitrobenzene etc.), halogenated hydrocarbon solvents (e.g., dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride etc.), ether solvents (e.g., ethyl ether, tetrahydrofuran, dioxane, diemthoxyethane etc.), nitroalkanes (e.g., nitromethane, propionitrile etc.), and carbon disulfide, with preference given to, dichloromethane, 1,2-dichloroethane, nitrobenzene, carbon disulfide and others. The amount of solvent used is normally about 0.5 to about 100 ml, preferably about 5to about 20 ml per mmol of the compound (IIIa) or a salt thereof. Reaction temperature is normally about xe2x88x9230 to about 150xc2x0 C., preferably about 20 to about 100xc2x0 C. Reaction time is normally about 0.5 to about 72 hours, preferably about 1 to about 16 hours.
Lewis acids can be used in this rection if necessary. Such lewis acids include aluminum chloride, aluminum bromide, zinc chloride, titanium chloride, tin (IV) chloride, boron trifluoride, iron (II) chloride, iron (III) chloride, antimony (V) pentachloride, bismuth (III) chloride, mercury (II) chloride, hydrogen fluoride, sulfuric acid and polyphosphoric acid, with preference given to aluminum chloride and others. The amount of Lewis acid used is normally about 1 to about 10 mol, preferably about 2 to about 10 mol per mol of the compound (IIIa) or a salt thereof. The amount of the compound (IIa) or a salt thereof used is normally about 1 to about 20 mol. preferably about 1 to about 5mol per mol of the compound (IIIa) or a salt thereof.
In the above reaction, the position at which the following group: 
in the compound (IIIa) or a salt thereof is introduced to the compound (IIa) or a salt thereof may be any one of the possible positions of substitution in benzene ring in the compound (IIa). However, it is introduced mainly at the 7-position. However, compounds having an introduction at other positions (6, or 9-positions) may be produced and separated.
Protecting groups for the amino group represented as W, for example, include the hydrocarbon group which may be substituted and the acyl groups, specifically, an acyl group such as a formyl group, a C1-6 alkyl-carbonyl group which may be substituted (e.g. acetyl, ethylcarbonyl etc.), a benzoyl group, a C1-6 alkyl-oxycarbonyl group (e.g. methoxycarbonyl, ethoxycarbonyl etc.), a phenyloxycarbonyl group (e.g. phenoxycarbonyl etc.), a C7-15 aralkylbxy-carbonyl group (e.g. benzyloxycarbonyl, fluorenyloxycarbonyl etc.), a hydrocarbon group such as a trityl group and a phthaloyl group. Substituents for these protecting groups include halogen (e.g., fluorine, chlorines bromine, iodine etc.), C1-6 alkyl-carbonyl (e.g., methylcarbonyl, ethylcarbonyl, butylcarbonyl etc.) and nitro, the number of substituents being about 1 to about 3.
With respect to the above reactions, provided that the starting material compound has an amino group, a carboxyl group, a hydroxy group or another group as a substituent therefor, such substituent may have a protecting group in common use in peptide chemistry etc. as introduced therein. The desired compound can be obtained by removing the protecting group as necessary upon completion of the reaction.
Protecting groups for the amino group is the group represented as W hereinbefore and so on.
Protecting groups for the carboxyl group include a C1-6 alkyl group which may be substituted (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl etc.), a phenyl group, a trityl group, and a silyl group. Substituents for these protecting groups include halogen (e.g. fluorine, chlorine, bromine or iodine etc.), formyl, C1-6 alkyl-carbonyl (e.g., methylcarbonyl, ethylcarbonyl, butylcarbonyl etc.) and nitro, the number of substituents being about 1 to about 3.
Protecting groups for the hydroxyl group include a c1-6 alkyl group which may be substituted (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl etc.), a phenyl group, a C7-10 aralkyl group (e.g. benzyl etc.), a formyl group,a C1-6 alkylcatbdnyl group (e.g., acetyl, ethylcarbonyl etc.), a phenyloxycarbonyl group (e.g. phenoxycarbonyl etc.), a C7-10 aralkyl-carbonyl group (e.g. benzyloxycarbonyl etc.), a pyranyl group, a furanyl group and a silyl group. Substituents for these protecting groups include halogen (e.g. fluorine, chlorine, bromine, iodine etc.), C1-6 alkyl, phenyl, C7-10 aralkyl and nitro, the number of substituents being about 1 to 4.
These protecting groups can be removed by known methods or modifications thereof, including treatments with acid, base, reducing agents, ultraviolet rays, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride and palladium acetate.
When the compound (Ia2) or a salt thereof thus obtained, can be converted to a compound (Ia2: R6=H) or a salt thereof, by removing the protecting group with the known method or its modifications such as thereof, including treatments with acid, base, reducing agents, ultraviolet rays, hydrazine, phenylhydrazine, sodium N-methyldithiocarbamate, tetrabutylammonium fluoride and palladium acetate.
More specificaly, when the protecting group for the compound (Ia2) represented by W, is an acyl group, the protectiong group can be removed by deacylation described below. That is, the compound (Ia2) or a salt thereof, is kept at a temperature of normally about 10 to about 150xc2x0 C., preferably about 50 to about 100xc2x0 C., in an aqueous solution of an acid such as a mineral acid (e.g., nitric acid, hydrochloric acid, hydrobromic acid, iodic acid, sulfuric acid etc.) or a base such as an alkaline metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, barium hydroxide, lithium hydroxide etc.). The amount of such acid or base used is normally about 1 to about 100 mol, preferably about 1 to about 40 mol per mol of the compound (IIa) or a salt thereof. The strength of acid or base is normally about about 0.1 to about 10 N, preferably about 2 to about 10 N. Although varying depending on reaction temperature, reaction time is normally about 1 to about 24 hours, preferably about 2 to about 10 hours.
The compound (Ia2) in which R1 is an acyl group, or a salt thereof, can be converted to the compound (Ia2: R1=H) or a salt thereof by deacylation. The condition of deacylation is similar to the case that the protecting group of the amino group represented by W, is an acyl group.
The compound (Ia2) having an acylamino group which may be substituted, or a salt thereof, can be converted to the compound (Ia2) having a primary or secondary amino group, or a salt thereof, by deacylation. The condition of deacylation is similar to the case that the protecting group of the amino group represented by W, is an acyl group.
When the compound (Ia2) wherein R6 is a hydrogen atom (Ia2: R6=H) or a salt thereof is obtained, it can be converted to a compound (Ia2) wherein R6 is not a hydrogen atom by the reaction with the compound of the formula:
R6axe2x80x94Z1a
wherein Z1a represents a leaving group; R6a represents a hydrocarbon group which may be substituted or an acyl group.
When the compound (Ia2) wherein R1 is a hydrogen atom (Ia2: R1=H) or a salt thereof is obtained, it can be converted to a compound (Ia2) wherein R1 is not a hydrogen atom by the reaction with the compound of the formula:
R1axe2x80x94Z1a
wherein Z1a represents a leaving group; R1a represents a hydrocarbon group which may be substituted or an acyl group.
When the compound (Ia2) having a primary or secondary amino group or a salt thereof is obtained, it can be converted to a compound (Ia2) in which the amino group is substituted by R7, by the reaction with the compound of the formula:
R7xe2x80x94Z3
wherein Z3 represents a leaving group; R7 represents a hydrocarbon group which may be substituted.
The xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d and the xe2x80x9cacyl groupxe2x80x9d mentioned as R1a include but are not limited the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d and the xe2x80x9cacyl groupxe2x80x9d mentioned as R1.
The xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d and the xe2x80x9cacyl groupxe2x80x9d mentioned as R6a include but are not limited the xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d and the xe2x80x9cacyl groupxe2x80x9d mentioned as R6.
The xe2x80x9chydrocarbon group which may be substitutedxe2x80x9d mentioned as R7 include but are not limited the hydrocarbon group which may be substitutedxe2x80x9d mentioned as R1 or R6.
The leaving groups for Z1a and Z3 are exemplified by a halogen atoms (e.g. chlorine, bromine and iodine etc.), a C1-6 alkylsulfonyloxy group (e.g. methanesulfonyloxy, ethanesulfonyloxy etc.) or a C6-10 arylsufonyloxy group (e.g. benzenesulfonyloxy, p-toluenesulfonyloxy etc.), with preference given to methanesulfonyloxy, or a halogen atom (e.g. chlorine, bromine etc.) and others.
This reaction can be carried out in the presence or absence of a solvent, if necessary, with a base. Bases for this purpose include inorganic bases such as sodium carbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide and sodium hydride, and organic bases such as pyridine, 4-dimethylaminopyridine and triethylamine. Any solvent can be used, as long as it does not interfere with the reaction. Such solvents include lower alcohols such as methanol, ethanol, propanol, isopropanol, n-butanol and t-butanol, ethers such as dioxane, ether and tetrahydrofuran, aromatic hydrocarbons such as toluene, benzene and xylene, halogenated hydrocarbons such dichloromethane, 1,2-dichloroethane, amides such as dimethylformamide, dimethylacetamide and hexamethylphosphonotriamide, esters such as ethyl acetate and butyl acetate, nitrites such as acetonitrile and propionitrile.
This reaction can be carried out under cooling conditions"" (about 0 to about 10xc2x0 C.), at room temperature (about 10 to about 40xc2x0 C.) or under heating conditions (about 40 to about 120xc2x0 C.). Reaction time is normally about 10 minutes to about 48 hours, preferably about 2 to about 16 hours. The amount of compounds of formula: R6axe2x80x94Z1a, R1axe2x80x94Z1a or R7xe2x80x94Z3 used is preferably about 0.3 to about 5.0 mol per mol of the compound (Ia2) or a salt thereof. The amount of base used is normally about 1 or more mol, preferably about 1.1 to about 5 mol per mol of the compound (Ia2) or a salt thereof.
Also this reaction may be accelerated as appropriate in the presence of an iodide such as sodium iodide, potassium iodide or lithium iodide. In this case, the amount of iodide used is normally about 1 to about 5 mol, preferably about 1.1 to about 1.5 mol per mol of the compounds of formula: R6axe2x80x94Z1a, R1axe2x80x94Z1a or R7xe2x80x94Z3 
The compounds of formula: R6axe2x80x94, Z1a, R1axe2x80x94Z1a or R7xe2x80x94Z3 can be produced by known method or modifications thereof.
The starting material compound (Ia2) or a salt thereof may be used after isolation and purification by known means such as concentration, liquid property conversion, redissolution, solvent extraction, fractional distillation, distillation, crystallization, recrystallization and chromatography, or may be used in the form of a reaction mixture as such, without isolation, as a starting material.
The compound (Ia2) thus obtained can be converted to a salt by a conventional method when it is in a free form, and can be converted to a free form or another salt by a conventional method when it is in a salt form. The compound (Ia2) or a salt thereof can be isolated and purified by known methods as described above. Also, the compound (Ia2) or a salt thereof involves stereoisomers based on the presence of asymmetric carbon atoms. These isomers can also be isolated and purified by known methods as described above or other methods such as fractional recrystallization, and chromatography using optically active columns.
The above compound (I), inclusive of its salt, acts on the peripheral adipocytes of mammals (e.g. man, macacus, mouse, rat, canine, feline, bovine, etc.) to express intraadipocyte cAMP-increasing, lipolysis accelerating, and thermogenesis accelerating effects and, as, such, show remarkable body weight reducing (strictly, adipose mass-reducing) and body weight gain-suppressive effects.
The pharmacologic activity of compound (I), inclusive of its salt, is well isolated from its CNS activity as compared with the known centrally-acting anorectics such as mazindol. Thus, compound (I), inclusive of its salt, is characterized by low toxicity, with no central action at all or only a very slight central action. Moreover, the compound expresses marked efficacy in an oral regimen. The acute toxicity (LD50) of the compound (I) or salt according to the present invention is not less than about 100 mg/kg.
Therefore,the compound (I) inclusive of its salt can be used with advantage as a safe prophylactic and/or treating drug for obesity (adiposis), obesity-associated diseases, and complications of obesity in man and other mammals.
The disease in which the compound (I) or salt of the invention can be indicated includes but is not limited to: (1) obesity, (2) obesity-associated diseases such as (i) diabetes (particularly non-insulin-dependent diabetes), (ii) hyperlipemia, (iii) atherosclerosis, (iv) hypertension, and (3) complications of obesity such as (i) glucose tolerance abnormality, (ii) hyperinsulinemia, (iii) hypoHDL emia, (iv) hyperuricemia, (v) gout, (vi) angina pectoris, (vii) myocardial infarction, (viii) cardiac. dysfunction, (ix) hypercardia, (x) heart failure, (xi) chronic nephritis, (xii) Pickwick""s syndrome, (xiii) sleep apnea syndrome, (xiv) fatty liver, (xv) cholelithiasis, (xvi) pancreatitis, (xvii) arthritis deformans, (xviii) spondylolisthes is, (xix) hypoovarianism, (xx) emmeniopathy, (xxi) sterility, (xxii) tonsilar hypertrophy, (xxiii) parotid intumescence, and so forth. Particularly, the above compound (I) inclusive of its salt can be used with advantage in the prevention or treatment of obesity and non-insulin-dependent diabetes.
The above compound (I) inclusive of its salt can be safely administered, either as it is or as a pharmaceutical dosage form prepared using a pharmacologically acceptable carrier, for example, tablets (inclusive of dragees, film-coated tablets, etc.), powders, granules, capsules (inclusive of soft capsules), solutions, injections, suppositories, timed-release preparations, etc., either orally or parenterally (e.g. locally, rectally or intravenously) to man and other mammals. The content of compound (I) or a salt thereof in the dosage form of the invention is about 0.1 to about 100 weight % of the whole composition. Compound (I) inclusive of its salt according to the invention is usually formulated with a medicinally acceptable carrier, vehicle, or excipient and administered orally or parenterally to man and other mammals.
The dosage depends on the recipient""s background, route of administration, type of disease to be treated, clinical status and symptoms, and other factors. For use as an antiobese drug, for instance, in a human adult (body weight ca 70 kg), the recommended daily dosage is about 0.01-10,000 mg, preferably about 0.1 to about 2,000 mg, more preferably about 0.5 to about 1,000 mg, and still more preferably about 25 to about 500 mg, in terms of the active compound (Compound (I) or its salt). The above dosage can be administered once or in 2 to 4 divided doses daily.
As the pharmaceutically acceptable carrier mentioned above, various organic and inorganic carriers which are conventional as pharmaceutical preparation material can be employed. Such the carrier includes but is not limited to the excipient, lubricant, binder, and disintegrator for solid dosage forms and the solvent, solubilizer, suspending agent, isotonizing agent, buffer and local anesthetic for liquid dosage forms. Where necessary, various pharmaceutical additives such as the preservative, antioxidant, coloring agent, sweetener, adsorbent, wetting agent, etc. can also be included in formulations.
The preferred excipient includes but is not limited to lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, and light silicic anhydride. The preferred lubricant includes but is not limited to magnesium stearate, calcium stearate, talc, and colloidal silica.
The preferred binder includes but is not limited to crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, and carboxymethylcellulose sodium.
The preferred disintegrator includes but is not limited to starch, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, carboxymethylstarch sodium, and L-hydroxypropylcellulose.
The preferred solvent includes but is not limited to water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, etc.
The preferred solubilizer includes but is not limited to polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, and sodium citrate.
The preferred suspending agent includes but is not limited to surfactants such as stearoyltriethanolamide, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, etc. and hydrophilic macromolecular substances such as polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose sodium, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.
The preferred isotonizing agent includes but is not limited to glucose, D-sorbitol, sodium chloride, glycerin, and D-mannitol.
The preferred buffer includes but is not limited to phosphate, acetate, carbonate, citrate, and other buffers.
A preferred example of said local anesthetic is benzyl alcohol.
The preferred antiseptic includes but is not limited to p-hydroxybenzoic esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, and sorbic acid.
The preferred antioxidant includes but is not limited to salts of sulfurous acid, ascorbic acid, etc.